The DOI matches its Crossref record; 252 of the 258 references it cites were found in a registry or an index; 25 of the 520 sources its claims cite were checked for support.
Heme Synthesis and Acquisition in Bacterial Pathogens
Open accessAbstract
Bacterial pathogens require the iron-containing cofactor heme to cause disease. Heme is essential to the function of hemoproteins, which are involved in energy generation by the electron transport chain, detoxification of host immune effectors, and other processes. During infection, bacterial pathogens must synthesize heme or acquire heme from the host; however, host heme is sequestered in high-affinity hemoproteins. Pathogens have evolved elaborate strategies to acquire heme from host sources, particularly hemoglobin, and both heme acquisition and synthesis are important for pathogenesis. Paradoxically, excess heme is toxic to bacteria and pathogens must rely on heme detoxification strategies. Heme is a key nutrient in the struggle for survival between host and pathogen, and its study has offered significant insight into the molecular mechanisms of bacterial pathogenesis.
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Claims the paper makes
272 Not checked yet · 48 Own interpretation · 11 No basis given · 7 Partly supported · 2 Not supported · 1 Supported so far · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“it is incapable of synthesizing heme”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Disputedcites [167] Granick S Gilder H The porphyrin requirements of Haemophilus influenzae and some functions of the vinyl and propionic acid side chains of heme J Gen Physiol 30 1946 1 13 20997746 sourceExperimental — accuracy not yet measured
The Experiments section reports that H. influenzae converts supplied protoporphyrin into iron protoporphyrin (heme) by inserting iron. The paper shows that the organism needs a supplied porphyrin precursor, not that it is incapable of forming heme. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“a high-affinity HpuB-Hb complex requires the presence of HpuA”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Disputedcites [196] Chen CJ Elkins C Sparling PF Phase variation of hemoglobin utilization in Neisseria gonorrhoeae Infect Immun 66 1998 987 993 9488386 PMC108006 sourceExperimental — accuracy not yet measured
The Results (p. 4) report that HpuB still bound hemoglobin in the absence of HpuA, and the Discussion (p. 5) says HpuA’s absence had no obvious effect on HpuB’s hemoglobin binding. The paper does not establish a requirement for HpuA to form a high-affinity HpuB–hemoglobin complex; it instead identifies HpuA as necessary for hemoglobin utilization for growth. (LLM, conf=0.80)
Checked by a reasoning model — may be wrong.
- Disputedcites [197] Rohde KH Dyer DW Analysis of haptoglobin and hemoglobin –haptoglobin interactions with the Neisseria meningitidis TonB-dependent receptor HpuAB by flow cytometry Infect Immun 72 2004 2494 2506 15102756 PMC387877 sourceExperimental — accuracy not yet measured
The Results section (‘Flow cytometric analysis of HpuAB-Hb binding kinetics’) reports that HpuB alone bound Hb with near-wild-type affinity (Kd 409 nM versus 555 nM for HpuAB). HpuA was required for wild-type binding capacity and subsequent heme-iron uptake, not for the reported binding affinity. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“most bacteria (Alphaproteo-bacteria are the exception), archaea, and plants synthesize ALA from charged glutamyl-tRNAGlu via the “C5 pathway” (Fig. 1) [21,34,35].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [21] Hamza I Dailey HA One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans Biochim Biophys Acta 2012 1823 1617 1632 PMC3412874 22575458
- Partly supportedcites [34] Dailey HA Gerdes S Dailey TA Burch JS Phillips JD Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin Proc Natl Acad Sci USA 112 2015 2210 2215 25646457 PMC4343137 sourceExperimental — accuracy not yet measured
The paper’s introductory passage describes glutamyl-tRNA-based ALA synthesis as the five-carbon pathway and says it is the most prevalent route across all forms of life. It does not specify the citing sentence’s taxonomic breakdown or identify Alphaproteobacteria as an exception. The verbatim citing sentence includes archaea and plants; it does not except them. (LLM, conf=0.82)
- Not checked yetcites [35] Beale SI Gough SP Granick S Biosynthesis of delta-aminolevulinic acid from the intact carbon skeleton of glutamic acid in greening barley Proc Natl Acad Sci USA 72 1975 2719 2723 1058487 PMC432842 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Corynebacterium diphtheriae, a member of the Actinobacteria phylum, encodes two heme-responsive two-component systems (TCS).”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [71] Frunzke J Gatgens C Brocker M Bott M Control of heme homeostasis in Corynebacterium glutamicum by the two-component system HrrSA J Bacteriol 193 2011 1212 1221 21217007 PMC3067591 source
- Supportedcites [72] Bibb LA Kunkle CA Schmitt MP The ChrA–ChrS and HrrA–HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae Infect Immun 75 2007 2421 2431 17353293 PMC1865786 source
The Abstract identifies ChrA-ChrS and HrrA-HrrS as two-component systems in C. diphtheriae and reports that both are required for full hemoglobin-dependent activation of the hmuO promoter. It also links both systems to regulation of heme homeostasis, supporting the description of them as heme-responsive. (LLM, conf=0.92)
- Supportedcites [73] Bibb LA Schmitt MP The ABC transporter HrtAB confers resistance to hemin toxicity and is regulated in a hemin-dependent manner by the ChrAS two-component system in Corynebacterium diphtheriae J Bacteriol 192 2010 4606 4617 20639324 PMC2937406 source
The passage labeled Abstract (page not provided) identifies ChrAS and HrrAS as two-component systems in C. diphtheriae. It states that both participate in heme-dependent regulation of gene expression. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“C. diphtheriae utilizes non-NEAT-mediated heme uptake systems for heme-iron acquisition, termed HmuTUV, HtaABC, and ChtABC/CirA.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [144] Schmitt MP Utilization of host iron sources by Coryne-bacterium diphtheriae: identification of a gene whose product is homologous to eukaryotic heme oxygenases and is required for acquisition of iron from heme and hemoglobin J Bacteriol 179 1997 838 845 9006041 PMC178768 source
- Not checked yetcites [145] Drazek ES Hammack CA Schmitt MP Corynebacterium diphtheriae genes required for acquisition of iron from haemin and haemoglobin are homologous to ABC haemin transporters Mol Microbiol 36 2000 68 84 10760164 source
- Could not verifycites [146] Thompson JM Jones HA Perry RD Molecular characterization of the hemin uptake locus (hmu) from Yersinia pestis and analysis of hmu mutants for hemin and hemoprotein utilization Infect Immun 67 1999 3879 3892 10417152 PMC96668 sourceExperimental — accuracy not yet measured
The Discussion describes HmuTUV-mediated heme uptake in Yersinia pestis, not C. diphtheriae. Searches for C. diphtheriae, HtaABC, ChtABC/CirA, and non-NEAT uptake found no passage in our copy addressing the claimed systems in C. diphtheriae. (LLM, conf=0.78)
- Not checked yetcites [147] Allen CE Schmitt MP HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae J Bacteriol 191 2009 2638 2648 19201805 PMC2668399 source
- Not checked yetcites [148] Allen CE Schmitt MP Novel hemin binding domains in the Corynebacterium diphtheriae HtaA protein interact with hemoglobin and are critical for heme iron utilization by HtaA J Bacteriol 193 2011 5374 5385 21803991 PMC3187408 source
- Partly supportedcites [149] Draganova EB Akbas N Adrian SA Lukat-Rodgers GS Collins DP Dawson JH Heme binding by Corynebacterium diphtheriae HmuT: function and heme environment Biochemistry 54 2015 6598 6609 26478504 PMC4943319 sourceExperimental — accuracy not yet measured
The paper’s heme-uptake discussion (page unavailable) describes HmuTUV and the heme-binding roles of HtaA and HtaB in C. diphtheriae. It does not identify HtaABC as a separate system or mention ChtABC/CirA, so it does not support the full list of systems attributed to it. (LLM, conf=0.86)
- Partly supportedcites [150] Kunkle CA Schmitt MP Analysis of a DtxR-regulated iron transport and siderophore biosynthesis gene cluster in Corynebacterium diphtheriae J Bacteriol 187 2005 422 433 15629913 PMC543566 sourceExperimental — accuracy not yet measured
The References (no page available) identify work on C. diphtheriae genes required to acquire iron from hemin and hemoglobin, supporting the broad heme-iron acquisition point. The paper’s Results and Discussion instead examine siderophore transport; the passages found do not identify HmuTUV, HtaABC, or ChtABC/CirA or establish that they are non-NEAT-mediated. (LLM, conf=0.78)
- Partly supportedcites [151] Kunkle CA Schmitt MP Analysis of the Corynebacterium diphtheriae DtxR regulon: identification of a putative siderophore synthesis and transport system that is similar to the Yersinia high-pathogenicity island-encoded yersiniabactin synthesis and uptake system J Bacteriol 185 2003 6826 6840 14617647 PMC262719 sourceExperimental — accuracy not yet measured
The Discussion identifies HmuTUV as an ABC heme transport system and describes HtaA and ChtA as possible heme-transport-associated proteins. It says HtaA’s function in C. diphtheriae is unknown and ChtB’s function is unknown; it does not establish that all three named systems are used for heme-iron acquisition or characterize them as non-NEAT-mediated. No page number is available in our copy. (LLM, conf=0.86)
- Partly supportedcites [152] Allen CE Burgos JM Schmitt MP Analysis of novel iron-regulated, surface-anchored hemin-binding proteins in Corynebacterium diphtheriae J Bacteriol 195 2013 2852 2863 23585541 PMC3697262 sourceExperimental — accuracy not yet measured
The Introduction identifies HmuTUV as a hemin transporter and HtaA/HtaB as hemin-binding proteins whose domains lack significant similarity to NEAT domains. The Abstract identifies two other loci as ChtA-ChtB and ChtC-CirA, not a single ChtABC/CirA system. The paper does not identify an HtaABC system, and its results do not establish that ChtA or ChtC is required for hemin-iron use. (LLM, conf=0.87)
- Partly supportedcites [153] Allen CE Schmitt MP Utilization of host iron sources by Corynebacterium diphtheriae: multiple hemoglobin-binding proteins are essential for the use of iron from the hemoglobin– haptoglobin complex J Bacteriol 197 2015 553 562 25404705 PMC4285985 sourceExperimental — accuracy not yet measured
The Introduction identifies HmuTUV and the hemin-binding HtaA/HtaB proteins, distinguishes their CR domains from NEAT domains, and describes the chtA-chtB and cirA-chtC regions. The Results show that HmuTUV, HtaA, and either ChtA or ChtC contribute to acquiring iron from the hemoglobin–haptoglobin complex. However, the paper does not identify systems named “HtaABC” or “ChtABC/CirA”; it describes different gene groupings and does not establish all the named components as separate heme-iron uptake systems. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“P. aeruginosa encodes direct and indirect systems for heme uptake.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Could not verifycites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 sourceExperimental — accuracy not yet measured
The section “Regulation in other bacteria” says P. aeruginosa has 34 TonB-dependent transporters and discusses its siderophore uptake, but does not identify heme-uptake systems. The section “The twelve TBDTs are structurally similar” discusses heme transporters generally, without linking direct and indirect heme uptake to P. aeruginosa. Searches for heme uptake, direct and indirect systems, and PhuR/HasR found no passage establishing the claim. (LLM, conf=0.72)
- Partly supportedcites [155] Letoffe S Nato F Goldberg ME Wandersman C Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR Mol Microbiol 33 1999 546 555 10417645 sourceExperimental — accuracy not yet measured
The Introduction states that P. aeruginosa uses the extracellular haem-binding protein HasA for haem uptake, supporting the indirect-system part of the claim. It describes direct receptor binding as widespread among bacteria but does not establish a direct haem-uptake system in P. aeruginosa. The separate finding that HasR alone permits uptake concerns S. marcescens components reconstituted in E. coli, not P. aeruginosa. (LLM, conf=0.86)
- Partly supportedcites [156] Letoffe S Deniau C Wolff N Dassa E Delepelaire P Lecroisey A Haemophore-mediated bacterial haem transport: evidence for a common or overlapping site for haem-free and haem-loaded haemophore on its specific outer membrane receptor Mol Microbiol 41 2001 439 450 11489129 sourceExperimental — accuracy not yet measured
The Introduction identifies a HasA haemophore in P. aeruginosa, supporting an indirect haem-uptake route. The Introduction and Discussion describe haemophore-dependent and direct uptake through HasR, but those passages concern the Serratia marcescens system; they do not establish that P. aeruginosa encodes a direct uptake system. (LLM, conf=0.83)
- Supportedcites [157] Smith AD Wilks A Differential contributions of the outer membrane receptors PhuR and HasR to heme acquisition in Pseudomonas aeruginosa J Biol Chem 290 2015 7756 7766 25616666 PMC4367277 source
The paper describes two heme-uptake systems in P. aeruginosa: PhuR transports heme through the outer membrane, while the secreted hemophore HasA captures heme and transfers it to HasR (section labeled Abstract; page unavailable). These correspond to direct and indirect uptake. (LLM, conf=0.92)
- Supportedcites [158] Oglesby-Sherrouse AG Vasil ML Characterization of a heme-regulated non-coding RNA encoded by the prrF locus of Pseudomonas aeruginosa PLoS One 5 2010 e9930 20386693 PMC2851614 source
The Introduction describes two P. aeruginosa heme-uptake systems: Phu has a receptor that binds heme, while Has uses a secreted hemophore to scavenge it. This supports the distinction between direct and indirect uptake. (LLM, conf=0.93)
- Partly supportedcites [159] Reinhart AA Powell DA Nguyen AT O'Neill M Djapgne L Wilks A The prrF-encoded small regulatory RNAs are required for iron homeostasis and virulence of Pseudomonas aeruginosa Infect Immun 83 2015 863 875 25510881 PMC4333466 sourceExperimental — accuracy not yet measured
The Introduction says P. aeruginosa can acquire heme, and reference 11 names two distinct heme-uptake systems, phu and has. Our copy does not describe those systems as direct and indirect, so that distinction is not supported by this source. (LLM, conf=0.82)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recently, small regulatory RNAs have been described that impact phuS mRNA levels, suggesting another layer of heme-responsive regulation [158,159]”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Partly supportedcites [158] Oglesby-Sherrouse AG Vasil ML Characterization of a heme-regulated non-coding RNA encoded by the prrF locus of Pseudomonas aeruginosa PLoS One 5 2010 e9930 20386693 PMC2851614 sourceExperimental — accuracy not yet measured
The Results section reports heme-responsive PrrH and suggests that it affects expression of other mRNAs, including nirL and m-acnA. The Introduction discusses PhuS’s role in heme handling, but our copy does not report that a small RNA affects phuS mRNA levels (searched: phuS mRNA levels, phuS regulation, phuS). (LLM, conf=0.85)
- Supportedcites [159] Reinhart AA Powell DA Nguyen AT O'Neill M Djapgne L Wilks A The prrF-encoded small regulatory RNAs are required for iron homeostasis and virulence of Pseudomonas aeruginosa Infect Immun 83 2015 863 875 25510881 PMC4333466 source
The Results passage reports that phuS expression increases in the mutant lacking prrF-encoded sRNAs and returns to wild-type levels when complemented. It concludes that the data are consistent with heme modulating phuS mRNA levels via the PrrH sRNA; the mechanism remains a proposed model. Page numbers are not provided in our copy. (LLM, conf=0.93)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The HxuCBA system, described primarily in H. influenzae type B, is capable of heme acquisition from free heme and heme-hemopexin (Hx).”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [169] Cope LD Thomas SE Hrkal Z Hansen EJ Binding of heme-hemopexin complexes by soluble HxuA protein allows utilization of this complexed heme by Haemophilus influenzae Infect Immun 66 1998 4511 4516 9712810 PMC108548 source
- Not checked yetcites [170] Cope LD Yogev R Muller-Eberhard U Hansen EJ A gene cluster involved in the utilization of both free heme and heme: hemopexin by Haemophilus influenzae type b J Bacteriol 177 1995 2644 2653 7751272 PMC176933 source
- Partly supportedcites [171] Baelen S Dewitte F Clantin B Villeret V Structure of the secretion domain of HxuA from Haemophilus influenzae Acta Crystallogr Sect F: Struct Biol Cryst Commun 69 2013 1322 1327 PMC3855712 24316822 sourceExperimental — accuracy not yet measured
The Introduction describes HxuA binding haem–haemopexin and releasing haem for uptake through HxuC, supporting acquisition from that complex. It does not say the system acquires haem from free haem as a separate source, or limit the description primarily to H. influenzae type B. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“their involvement in resisting heme toxicity is clear.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Partly supportedcites [146] Thompson JM Jones HA Perry RD Molecular characterization of the hemin uptake locus (hmu) from Yersinia pestis and analysis of hmu mutants for hemin and hemoprotein utilization Infect Immun 67 1999 3879 3892 10417152 PMC96668 sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports a suggestion that HemS reduces heme toxicity in E. coli under a specific high-copy-number plasmid condition. But the authors observed no deleterious effects in their Y. pestis hmuS mutant and say HmuS’s role remains enigmatic, so the source does not establish that resistance to heme toxicity is a clear role of the protein family. (LLM, conf=0.87)
- Supportedcites [160] Lansky IB Lukat-Rodgers GS Block D Rodgers KR Ratliff M Wilks A The cytoplasmic heme-binding protein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is an intracellular heme-trafficking protein to the delta-regioselective heme oxygenase J Biol Chem 281 2006 13652 13662 16533806 source
The introduction (p. 1) says HemS was essential in preventing heme toxicity in Yersinia. The Discussion (p. 9) reports heme toxicity in a ShuS knockout at high heme concentrations that was reversed by restoring ShuS. The paper notes that the proteins may differ in how essential they are for protection. (LLM, conf=0.89)
- Supportedcites [225] Wyckoff EE Lopreato GF Tipton KA Payne SM Shigella dysenteriae ShuS promotes utilization of heme as an iron source and protects against heme toxicity J Bacteriol 187 2005 5658 5664 16077111 PMC1196095 source
The Results section reports that ShuS prevented growth inhibition at high hemin concentrations, and the Discussion says this suggests ShuS can reduce the toxicity of transported heme. The paper also reports a protective effect for its homologue HemS under a specific experimental condition; it does not establish that every family member protects against heme toxicity. (LLM, conf=0.90)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
In the paper
“Pathogens have evolved elaborate strategies to acquire heme from host sources, particularly hemoglobin”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“During infection, bacterial pathogens must synthesize heme or acquire heme from the host; however, host heme is sequestered in high-affinity hemoproteins.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“pathogens must rely on heme detoxification strategies”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Heme is essential to the function of hemoproteins, which are involved in energy generation by the electron transport chain, detoxification of host immune effectors, and other processes.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“cells rely on heme for the function of many widely conserved enzymes including catalase, nitric oxide synthase, hemoglobin (Hb), and others”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
What the sources say
- Not checked yetcites [1] Chen JJ London IM Hemin enhances the differentiation of mouse 3T3 cells to adipocytes Cell 26 1981 117 122 6799206 source
- Not checked yetcites [2] Shelver D Kerby RL He Y Roberts GP CooA, a CO-sensing transcription factor from Rhodospirillum rubrum, is a CO-binding heme protein Proc Natl Acad Sci USA 94 1997 11216 11220 9326589 PMC23420 source
- Not checked yetcites [3] Faller M Matsunaga M Yin S Loo JA Guo F Heme is involved in microRNA processing Nat Struct Mol Biol 14 2007 23 29 17159994 source
- Not checked yetcites [4] Bonyhady RE Hendry IA Hill CE McLennan IS Effects of haemin on neurones derived from the neural crest Dev Neurosci 5 1982 125 129 6127199 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“excess heme is toxic to bacteria”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
What the sources say
- Not checked yetcites [25] Everse J Hsia N The toxicities of native and modified hemoglobins Free Radic Biol Med 22 1997 1075 1099 9034247 source
- Not checked yetcites [26] Anzaldi LL Skaar EP Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens Infect Immun 78 2010 4977 4989 20679437 PMC2981329 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Bacterial pathogens require the iron-containing cofactor heme to cause disease.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
What the sources say
- Not checked yetcites [84] Skaar EP Humayun M Bae T DeBord KL Schneewind O Iron-source preference of Staphylococcus aureus infections Science 305 2004 1626 1628 15361626 source
- Not checked yetcites [85] Pishchany G Sheldon JR Dickson CF Alam MT Read TD Gell DA IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus J Infect Dis 209 2014 1764 1772 24338348 PMC4038968 source
- Not checked yetcites [86] Pishchany G McCoy AL Torres VJ Krause JC Crowe JE Jr Fabry ME Specificity for human hemoglobin enhances Staphylococcus aureus infection Cell Host Microbe 8 2010 544 550 21147468 PMC3032424 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“host heme is sequestered in high-affinity hemoproteins”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
What the sources say
- Not checked yetcites [27] Smith A McCulloh RJ Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders Front Physiol 6 2015 187 26175690 PMC4485156 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“When Hb is released from erythrocytes or otherwise exists extracellularly, it is rapidly bound by haptoglobin (Hp) [27].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [27] Smith A McCulloh RJ Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders Front Physiol 6 2015 187 26175690 PMC4485156 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Free Hb and its modified forms, in the presence of reactive oxygen species, exhibit cytotoxic effects toward endothelial cells [29].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [29] Jeney V Balla J Yachie A Varga Z Vercellotti GM Eaton JW Pro-oxidant and cytotoxic effects of circulating heme Blood 100 2002 879 887 12130498 source
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In the paper
“Its abundance and location in erythrocytes make Hb a rich heme source for pathogens.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
- Not checked yetcites [24] Bridges KR Seligman PA Disorders of Iron Metabolism J.B Lippincott Company New York 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“free heme and Hb are toxic to the human host and bacterial pathogens alike [25,26]”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [25] Everse J Hsia N The toxicities of native and modified hemoglobins Free Radic Biol Med 22 1997 1075 1099 9034247 source
- Not checked yetcites [26] Anzaldi LL Skaar EP Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens Infect Immun 78 2010 4977 4989 20679437 PMC2981329 source
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In the paper
“an evolutionary arms race has developed at the host–pathogen interface involving host iron-binding proteins and the mechanisms bacteria encode to steal iron”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Bacterial pathogens have evolved high-affinity Hb-binding proteins for the acquisition of heme”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
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In the paper
“The solubility of ferric iron in aerobic solution is exceedingly low”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
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In the paper
“high-affinity iron-binding proteins, including transferrin, lactoferrin, albumin, and ferritin, sequester iron extracellularly and intracellularly”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
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In the paper
“For instance, free iron rarely exists in the mammalian host.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Under physiological conditions, HMB will spontaneously cyclize to form the uroporphyrinogen I isomer, a biosynthetic deadend.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [41] Jordan PM The biosynthesis of tetrapyrroles Elsevier New York, NY 1991
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Therefore, heme is at the center of a complex interplay between host and pathogen for survival.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The Gram-positive HemH, a coproporphyrin ferrochelatase, inserts ferrous iron to form coproheme [52].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [52] Lobo SA Scott A Videira MA Winpenny D Gardner M Palmer MJ Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway Mol Microbiol 97 2015 472 487 25908396 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“ALA dehydratase (also called porphobilinogen synthase; annotated as HemB) is responsible for the condensation of two ALA to porphobilinogen (PBG) [38].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [38] Hansson M Rutberg L Schroder I Hederstedt L The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes of the biosynthetic pathway from glutamate to uroporphyrinogen III J Bacteriol 173 1991 2590 2599 1672867 PMC207825 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The linear tetrapyrrole hydroxymethylbilane (HMB) is produced by a head-to-tail condensation and deamination of four PBG molecules, catalyzed by HMB synthase (alternatively called PBG deaminase, annotated as HemC) [39,40].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [39] Louie GV Brownlie PD Lambert R Cooper JB Blundell TL Wood SP Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site Nature 359 1992 33 39 1522882 source
- Not checked yetcites [40] Bung N Pradhan M Srinivasan H Bulusu G Structural insights into E. coli porphobilinogen deaminase during synthesis and exit of 1-hydroxymethylbilane PLoS Comput Biol 10 2014 e1003484 24603363 PMC3945110 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The third protoporphyrinogen oxidase is HemY, an FAD- and oxygen-dependent protoporphyrinogen oxidase found in some Proteobacteria as well as eukaryotes [50].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [50] Porra RJ Falk JE The enzymic conversion of coproporphyrinogen III into protoporphyrin IX Biochem J 90 1964 69 75 5832302 PMC1202522 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“It is now clear that Grampositive organisms utilize a unique series of terminal steps to synthesize heme (in green in Fig. 1).”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
boosted- Asserted: passes — The authors put it forward as true.
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In the paper
“Therefore, most bacteria utilize uroporphyrinogen III synthase (HemD) to catalyze the cyclization of HMB through a spiro-intermediate to form uroporphyrinogen III [41].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [41] Jordan PM The biosynthesis of tetrapyrroles Elsevier New York, NY 1991
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Protoporphyrinogen IX is subsequently oxidized to form proto-porphyrin IX, by a six-electron oxidation catalyzed by one of three protoporphyrinogen oxidase enzymes.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [48] Boynton TO Daugherty LE Dailey TA Dailey HA Identification of Escherichia coli HemG as a novel, menadione-dependent flavodoxin with protoporphyrinogen oxidase activity Biochemistry 48 2009 6705 6711 19583219 PMC2749469 source
- Not checked yetcites [49] Kobayashi K Masuda T Tajima N Wada H Sato N Molecular phylogeny and intricate evolutionary history of the three isofunctional enzymes involved in the oxidation of protoporphyrinogen IX Genome Biol Evol 6 2014 2141 2155 25108393 PMC4231631 source
- Not checked yetcites [50] Porra RJ Falk JE The enzymic conversion of coproporphyrinogen III into protoporphyrin IX Biochem J 90 1964 69 75 5832302 PMC1202522 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The final step of the classical pathway is the insertion of ferrous iron by protoporphyrin ferrochelatase (HemH) to form protoheme IX, called heme [51].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [51] Camadro JM Labbe P Purification and properties of ferrochelatase from the yeast Saccharomyces cerevisiae. Evidence for a precursor form of the protein J Biol Chem 263 1988 11675 11682 3042776 source
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In the paper
“In Gram-negative organisms, as well as eukaryotes, coproporphyrinogen III is converted to proto-porphyrinogen IX by coproporphyrinogen III oxidase. This step is the first of the terminal three steps in the classical heme synthesis pathway (in blue in Fig. 1) and is catalyzed by oxygen dependent HemF or by oxygen independent HemN [46,47].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [46] Troup B Hungerer C Jahn D Cloning and characterization of the Escherichia coli hemN gene encoding the oxygen-independent coproporphyrinogen III oxidase J Bacteriol 177 1995 3326 3331 7768836 PMC177029 source
- Not checked yetcites [47] Seehra JS Jordan PM Akhtar M Anaerobic and aerobic coproporphyrinogen III oxidases of Rhodopseudomonas spheroides. Mechanism and stereochemistry of vinyl group formation Biochem J 209 1983 709 718 6603215 PMC1154149 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“From ALA to heme, the steps of the classical synthesis pathway are shared by eukaryotes and Gram-negative bacteria.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“the terminal steps of heme synthesis in the Gram-positive phyla Firmicutes and Actinobacteria have been described with genomic and biochemical analysis and termed the non-canonical or transitional pathway [34,52].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [34] Dailey HA Gerdes S Dailey TA Burch JS Phillips JD Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin Proc Natl Acad Sci USA 112 2015 2210 2215 25646457 PMC4343137 source
- Not checked yetcites [52] Lobo SA Scott A Videira MA Winpenny D Gardner M Palmer MJ Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway Mol Microbiol 97 2015 472 487 25908396 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In bacteria, regulation has been recognized to occur largely at two steps, abundance of the initial enzyme HemA and transcription of the coproporphyrinogen oxidase enzymes.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [58–79]
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, coproheme is decarboxylated by HemQ, an enzyme unique to members of the Firmicutes and Actinobacteria to form protoheme IX [54–57].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [54] Mayfield JA Hammer ND Kurker RC Chen TK Ojha S Skaar EP The chlorite dismutase (HemQ) from Staphylococcus aureus has a redox-sensitive heme and is associated with the small colony variant phenotype J Biol Chem 288 2013 23488 23504 23737523 PMC5395028 source
- Not checked yetcites [55] Dailey HA Gerdes S HemQ: an iron-coproporphyrin oxidative decarboxylase for protoheme synthesis in Firmicutes and Actinobacteria Arch Biochem Biophys 574 2015 27 35 25711532 PMC4414794 source
- Not checked yetcites [56] Dailey TA Boynton TO Albetel AN Gerdes S Johnson MK Dailey HA Discovery and characterization of HemQ: an essential heme biosynthetic pathway component J Biol Chem 285 2010 25978 25986 20543190 PMC2923992 source
- Not checked yetcites [57] Celis AI Streit BR Moraski GC Kant R Lash TD Lukat-Rodgers GS Unusual peroxide-dependent, heme-transforming reaction catalyzed by HemQ Biochemistry 54 2015 4022 4032 26083961 PMC4950513 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the vital role of heme to bacterial physiology, the regulation of heme biosynthesis has not been well studied outside of a few model organisms.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In several species, hemF and hemN are regulated by different oxygen- or anaerobic-responsive regulators to ensure proper expression of oxygen-dependent or oxygen-independent coproporphyrinogen oxidases.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [74] Mancini S Imlay JA The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress Mol Microbiol 96 2015 744 763 25664592 PMC4430354 source
- Not checked yetcites [75] Marino M Ramos HC Hoffmann T Glaser P Jahn D Modulation of anaerobic energy metabolism of Bacillus subtilis by arfM (ywiD) J Bacteriol 183 2001 6815 6821 11698370 PMC95522 source
- Not checked yetcites [76] Hippler B Homuth G Hoffmann T Hungerer C Schumann W Jahn D Characterization of Bacillus subtilis hemN J Bacteriol 179 1997 7181 7185 9371469 PMC179663 source
- Not checked yetcites [77] Homuth G Rompf A Schumann W Jahn D Transcriptional control of Bacillus subtilis hemN and hemZ J Bacteriol 181 1999 5922 5929 10498703 PMC103618 source
- Not checked yetcites [78] Chen L Keramati L Helmann JD Coordinate regulation of Bacillus subtilis peroxide stress genes by hydrogen peroxide and metal ions Proc Natl Acad Sci USA 92 1995 8190 8194 7667267 PMC41122 source
- Not checked yetcites [79] Rompf A Hungerer C Hoffmann T Lindenmeyer M Romling U Gross U Regulation of Pseudomonas aeruginosa hemF and hemN by the dual action of the redox response regulators Anr and Dnr Mol Microbiol 29 1998 985 997 9767567 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The Clp and Lon proteases are responsible for this reduction in HemA levels [61].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [61] Wang L Elliott M Elliott T Conditional stability of the HemA protein (glutamyl-tRNA reductase) regulates heme biosynthesis in Salmonella typhimurium J Bacteriol 181 1999 1211 1219 9973348 PMC93499 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, ChrA can repress transcription of hemA in heme replete conditions [72,73].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [72] Bibb LA Kunkle CA Schmitt MP The ChrA–ChrS and HrrA–HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae Infect Immun 75 2007 2421 2431 17353293 PMC1865786 source
- Not checked yetcites [73] Bibb LA Schmitt MP The ABC transporter HrtAB confers resistance to hemin toxicity and is regulated in a hemin-dependent manner by the ChrAS two-component system in Corynebacterium diphtheriae J Bacteriol 192 2010 4606 4617 20639324 PMC2937406 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“With a few notable exceptions including Bartonella hensaela, Enterococcus faecalis, Haemophilus influenzae, and Streptococcus spp., most human pathogens encode complete heme biosynthetic pathways [80–83].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [80] Sander A Kretzer S Bredt W Oberle K Bereswill S Hemin-dependent growth and hemin binding of Bartonella henselae FEMS Microbiol Lett 189 2000 55 59 10913865 source
- Not checked yetcites [81] Frankenberg L Brugna M Hederstedt L Enterococcus faecalis heme-dependent catalase J Bacteriol 184 2002 6351 6356 12399505 PMC151946 source
- Not checked yetcites [82] Biberstein EL Mini PD Gills MG Action of Haemophilus cultures on δ-aminolevulinic acid J Bacteriol 86 1963 814 819 14066479 PMC278519 source
- Not checked yetcites [83] Baureder M Hederstedt L Heme proteins in lactic acid bacteria Adv Microb Physiol 62 2013 1 43 23481334 source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is likely that for many organisms, heme and terminal heme intermediates can have post-translational regulatory effects on heme synthesis enzymes.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“OxyR, a global regulator in E. coli, is responsible for the induction of oxygen-dependent hemF expression in hydrogen peroxide stress.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [74] Mancini S Imlay JA The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress Mol Microbiol 96 2015 744 763 25664592 PMC4430354 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these examples point to the transcriptional and post-translational control of HemA as a central step in heme synthesis regulation.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The response regulator HrrA directly binds the promoters of hemA, hemE, and hemH to repress their transcription in heme-replete conditions [71].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [71] Frunzke J Gatgens C Brocker M Bott M Control of heme homeostasis in Corynebacterium glutamicum by the two-component system HrrSA J Bacteriol 193 2011 1212 1221 21217007 PMC3067591 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The expression of coproporphyrinogen oxidase genes is the second major point of heme synthesis regulation.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [74] Mancini S Imlay JA The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress Mol Microbiol 96 2015 744 763 25664592 PMC4430354 source
- Not checked yetcites [75] Marino M Ramos HC Hoffmann T Glaser P Jahn D Modulation of anaerobic energy metabolism of Bacillus subtilis by arfM (ywiD) J Bacteriol 183 2001 6815 6821 11698370 PMC95522 source
- Not checked yetcites [76] Hippler B Homuth G Hoffmann T Hungerer C Schumann W Jahn D Characterization of Bacillus subtilis hemN J Bacteriol 179 1997 7181 7185 9371469 PMC179663 source
- Not checked yetcites [77] Homuth G Rompf A Schumann W Jahn D Transcriptional control of Bacillus subtilis hemN and hemZ J Bacteriol 181 1999 5922 5929 10498703 PMC103618 source
- Not checked yetcites [78] Chen L Keramati L Helmann JD Coordinate regulation of Bacillus subtilis peroxide stress genes by hydrogen peroxide and metal ions Proc Natl Acad Sci USA 92 1995 8190 8194 7667267 PMC41122 source
- Not checked yetcites [79] Rompf A Hungerer C Hoffmann T Lindenmeyer M Romling U Gross U Regulation of Pseudomonas aeruginosa hemF and hemN by the dual action of the redox response regulators Anr and Dnr Mol Microbiol 29 1998 985 997 9767567 source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Like Salmonella and E. coli, the Gram-positive bacterium Bacillus subtilis regulates levels of HemA.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [38] Hansson M Rutberg L Schroder I Hederstedt L The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes of the biosynthetic pathway from glutamate to uroporphyrinogen III J Bacteriol 173 1991 2590 2599 1672867 PMC207825 source
- Not checked yetcites [65] Schroder I Johansson P Rutberg L Hederstedt L The hemX gene of the Bacillus subtilis hemAXCDBL operon encodes a membrane protein, negatively affecting the steady-state cellular concentration of HemA (glutamyl-tRNA reductase) Microbiology 140 1994 731 740 8012594 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this manner, cellular levels of heme can regulate the first step of heme synthesis and limit the unnecessary synthesis of heme intermediates as well as the consumption of iron.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Recent metabolic engineering efforts to enhance ALA production in E. coli suggest that protoporphyrin IX post-translationally inhibits HemB, an additional example of feedback inhibition [64].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [64] Zhang J Kang Z Chen J Du G Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli Sci Rep 5 2015 8584 25716896 PMC4341193 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition to the regulation of HemA enzyme levels, the transcription of hemA is also a point of control for heme biosynthesis.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [66] Krieger R Rompf A Schobert M Jahn D The Pseudomonas aeruginosa hemA promoterisregulatedby Anr, Dnr, NarL and Integration Host Factor Mol Gen Genomics 267 2002 409 417 12073043 source
- Not checked yetcites [67] Hungerer C Troup B Romling U Jahn D Regulation of the hemA gene during 5-aminolevulinic acid formation in Pseudomonas aeruginosa J Bacteriol 177 1995 1435 1443 7883699 PMC176757 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, oxygen is a key regulatory of expression of coproporphyrinogen oxidase genes.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In B. subtilis, the transcription of coproporphyrinogen III oxidases hemN and hemZ (a second coproporphyrinogen oxidase, not to be confused with oxygen-dependent HemY) is induced anaerobically by the regulatory cascade of ResDE, Fnr, and YwiD to replace the oxygen-dependent HemY [75–78].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [75] Marino M Ramos HC Hoffmann T Glaser P Jahn D Modulation of anaerobic energy metabolism of Bacillus subtilis by arfM (ywiD) J Bacteriol 183 2001 6815 6821 11698370 PMC95522 source
- Not checked yetcites [76] Hippler B Homuth G Hoffmann T Hungerer C Schumann W Jahn D Characterization of Bacillus subtilis hemN J Bacteriol 179 1997 7181 7185 9371469 PMC179663 source
- Not checked yetcites [77] Homuth G Rompf A Schumann W Jahn D Transcriptional control of Bacillus subtilis hemN and hemZ J Bacteriol 181 1999 5922 5929 10498703 PMC103618 source
- Not checked yetcites [78] Chen L Keramati L Helmann JD Coordinate regulation of Bacillus subtilis peroxide stress genes by hydrogen peroxide and metal ions Proc Natl Acad Sci USA 92 1995 8190 8194 7667267 PMC41122 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that in C. diphtheriae, heme utilization is preferred over synthesis when exogenous heme is available.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“the membrane protein HemX post-transcriptionally regulates HemA abundance in B. subtilis [38,65].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [38] Hansson M Rutberg L Schroder I Hederstedt L The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes of the biosynthetic pathway from glutamate to uroporphyrinogen III J Bacteriol 173 1991 2590 2599 1672867 PMC207825 source
- Not checked yetcites [65] Schroder I Johansson P Rutberg L Hederstedt L The hemX gene of the Bacillus subtilis hemAXCDBL operon encodes a membrane protein, negatively affecting the steady-state cellular concentration of HemA (glutamyl-tRNA reductase) Microbiology 140 1994 731 740 8012594 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“During infection, S. aureus utilizes the leukocidins HlgAB and LukED to lyse erythrocytes and liberate Hb into the bloodstream [103].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [103] Spaan AN Reyes-Robles T Badiou C Cochet S Boguslawski KM Yoong P Staphylococcus aureus targets the Duffy Antigen Receptor for Chemokines (DARC) to lyse erythrocytes Cell Host Microbe 18 2015 363 370 26320997 PMC4578157 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, hemG was found to be important for Listeria mono-cytogenes oral infection [98].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [98] Cummins J Casey PG Joyce SA Gahan CG A mariner transposon-based signature-tagged mutagenesis system for the analysis of oral infection by Listeria monocytogenes PLoS ONE 8 2013 e75437 24069416 PMC3771922 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Outside of a few model pathogens, very little is understood regarding the regulation of heme synthesis, particularly during pathogenesis.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Current challenges and opportunities
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Transposon mutants lacking hemE in Acinetobacter baumannii were less effective at colonizing the murine lung [97].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [97] Wang N Ozer EA Mandel MJ Hauser AR Genomewide identification of Acinetobacter baumannii genes necessary for persistence in the lung mBio 5 2014 e01163 14 24895306 PMC4049102 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Transposon mutantsdisrupted in hemY were found to be defective for P. aeruginosa colonization of the murine gastrointestinal tract [95].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [95] Skurnik D Roux D Aschard H Cattoir V Yoder-Himes D Lory S A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas aeruginosa using high-throughput sequencing of transposon libraries PLoS Pathog 9 2013 e1003582 24039572 PMC3764216 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A mutant lacking hemB, also a heme-deficient SCV, demonstrates reduced colonization and bone destruction in a murine model of osteomyelitis [88,89].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [88] Hammer ND Cassat JE Noto MJ Lojek LJ Chadha AD Schmitz JE Inter- and intraspecies metabolite exchange promotes virulence of antibiotic-resistant Staphylococcus aureus Cell Host Microbe 16 2014 531 537 25299336 PMC4197139 source
- Not checked yetcites [89] von Eiff C Heilmann C Proctor RA Woltz C Peters G Gotz F A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly J Bacteriol 179 1997 4706 4712 9244256 PMC179315 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Importantly, the SCV phenotype is encountered clinically.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [89] von Eiff C Heilmann C Proctor RA Woltz C Peters G Gotz F A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly J Bacteriol 179 1997 4706 4712 9244256 PMC179315 source
- Not checked yetcites [90] Balwit JM van Langevelde P Vann JM Proctor RA Gentamicin-resistant menadione and hemin auxotrophic Staphylococcus aureus persist within cultured endothelial cells J Infect Dis 170 1994 1033 1037 7930701 source
- Not checked yetcites [91] Painter KL Strange E Parkhill J Bamford KB Armstrong-James D Edwards AM Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response Infect Immun 83 2015 1830 1844 25690100 PMC4399076 source
- Not checked yetcites [92] Sadowska B Bonar A von Eiff C Proctor RA Chmiela M Rudnicka W Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants FEMS Immunol Med Microbiol 32 2002 191 197 11934563 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Gram-positive pathogens, including S. aureus, Bacillus anthracis, and C. diphtheriae rely on heme acquisition during infection.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
- Not checked yetcites [125] Maresso AW Garufi G Schneewind O Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin PLoS Pathog 4 2008 e1000132 18725935 PMC2515342 source
- Not checked yetcites [144] Schmitt MP Utilization of host iron sources by Coryne-bacterium diphtheriae: identification of a gene whose product is homologous to eukaryotic heme oxygenases and is required for acquisition of iron from heme and hemoglobin J Bacteriol 179 1997 838 845 9006041 PMC178768 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on these trans-poson library infections, heme synthesis is vital to the fitness of a variety of pathogens.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For the intracellular pathogen Brucella abortus, hemH is required for virulence in a murine model of brucellosis [94].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [94] Almiron M Martinez M Sanjuan N Ugalde RA Ferrochelatase is present in Brucella abortus and is critical for its intracellular survival and virulence Infect Immun 69 2001 6225 6230 11553564 PMC98755 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“During systemic infection, this mutant is highly defective at colonizing the murine heart and liver relative to wildtype S. aureus [87].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [87] Hammer ND Reniere ML Cassat JE Zhang Y Hirsch AO Hood MI Two heme-dependent terminal oxidases power Staphylococcus aureus organ-specific colonization of the vertebrate host mBio 4 2013 PMC3735196 23900169 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In these infections, genes with marked mutations that are recovered at a lower frequency from the infected tissue relative to growth in vitro are considered important to infection.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [95] Skurnik D Roux D Aschard H Cattoir V Yoder-Himes D Lory S A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas aeruginosa using high-throughput sequencing of transposon libraries PLoS Pathog 9 2013 e1003582 24039572 PMC3764216 source
- Not checked yetcites [96] Palace SG Proulx MK Lu S Baker RE Goguen JD Genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of Yersinia pestis in deep tissue mBio 2014 5 PMC4147864 25139902
- Not checked yetcites [97] Wang N Ozer EA Mandel MJ Hauser AR Genomewide identification of Acinetobacter baumannii genes necessary for persistence in the lung mBio 5 2014 e01163 14 24895306 PMC4049102 source
- Not checked yetcites [98] Cummins J Casey PG Joyce SA Gahan CG A mariner transposon-based signature-tagged mutagenesis system for the analysis of oral infection by Listeria monocytogenes PLoS ONE 8 2013 e75437 24069416 PMC3771922 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Bacterial pathogens utilize a variety of heme acquisition strategies during infection, ranging from surface receptors to secreted proteins that bind either heme or hemoproteins.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies
What the sources say
- Not checked yetcites [102–159]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Considering that in some niches host heme is available and can reach toxic levels, pathogens with the capacity to both steal and synthesize heme must regulate both pathways.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Current challenges and opportunities
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This is despite the observation over half a century ago that the rate of staphylococcal heme synthesis is modulated by exogenous heme [101].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Current challenges and opportunities
What the sources say
- Not checked yetcites [101] Jensen J The effect of heme on tetrapyrrol synthesis in a heme requiring Staphylococcus aureus Biochem Biophys Res Commun 8 1962 271 277 14451646 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In addition to B. abortus and S. aureus, the advent of whole genome in vivo analysis of mutants using techniques such as transposon-sequencing and signature tagged mutagenesis has highlighted the role of heme synthesis.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [95] Skurnik D Roux D Aschard H Cattoir V Yoder-Himes D Lory S A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas aeruginosa using high-throughput sequencing of transposon libraries PLoS Pathog 9 2013 e1003582 24039572 PMC3764216 source
- Not checked yetcites [96] Palace SG Proulx MK Lu S Baker RE Goguen JD Genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of Yersinia pestis in deep tissue mBio 2014 5 PMC4147864 25139902
- Not checked yetcites [97] Wang N Ozer EA Mandel MJ Hauser AR Genomewide identification of Acinetobacter baumannii genes necessary for persistence in the lung mBio 5 2014 e01163 14 24895306 PMC4049102 source
- Not checked yetcites [98] Cummins J Casey PG Joyce SA Gahan CG A mariner transposon-based signature-tagged mutagenesis system for the analysis of oral infection by Listeria monocytogenes PLoS ONE 8 2013 e75437 24069416 PMC3771922 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“The Iron-regulated surface determinant system (Isd), first described in S. aureus, is the paradigm for Gram-positive heme acquisition [102].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“hemN was found to be important for Yersinia pestis infection of deep tissue [96].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [96] Palace SG Proulx MK Lu S Baker RE Goguen JD Genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of Yersinia pestis in deep tissue mBio 2014 5 PMC4147864 25139902
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This organization allows heme transferred from surface Isd proteins to pass through the cell wall to the membrane by IsdC's single heme-binding NEAT domain.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The widely conserved ferric uptake regulator (Fur) is the principle regulator of the expression of heme acquisition systems in S. aureus.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“At the membrane, IsdDEF transit heme across the membrane and into the cytosol.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [114] Zhu H Xie G Liu M Olson JS Fabian M Dooley DM Pathway for heme uptake from human methemoglobin by the iron-regulated surface determinants system of Staphylococcus aureus J Biol Chem 283 2008 18450 18460 18467329 PMC2440603 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“To access host heme and hemoproteins, IsdB, IsdH, and IsdA are covalently attached to the peptidoglycan by the standard Sortase A cysteine transpeptidase [106].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [106] Mazmanian SK Liu G Ton-That H Schneewind O Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall Science 285 1999 760 763 10427003 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Alternatively, the heme oxygenases IsdG and IsdI degrade heme to release iron [115]”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [115] Skaar EP Gaspar AH Schneewind O IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus J Biol Chem 279 2004 436 443 14570922 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“IsdC transfers heme to the membrane-associated transporter IsdDEF for transit across the membrane.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [114] Zhu H Xie G Liu M Olson JS Fabian M Dooley DM Pathway for heme uptake from human methemoglobin by the iron-regulated surface determinants system of Staphylococcus aureus J Biol Chem 283 2008 18450 18460 18467329 PMC2440603 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“IsdC alone transfers heme to the IsdE of the IsdDEF transporter [114].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [114] Zhu H Xie G Liu M Olson JS Fabian M Dooley DM Pathway for heme uptake from human methemoglobin by the iron-regulated surface determinants system of Staphylococcus aureus J Biol Chem 283 2008 18450 18460 18467329 PMC2440603 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In iron-deplete conditions, Fur no longer represses its regulon, allowing the transcription of the isdB, isdA, isdC-DEFsrtBisdG, and isdI loci [102].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Heme is bound in a hydrophobic pocket with critical coordination by tyrosine residues in a YXXXY motif.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [104] Grigg JC Vermeiren CL Heinrichs DE Murphy ME Haem recognition by a Staphylococcus aureus NEAT domain Mol Microbiol 63 2007 139 149 17229211 source
- Not checked yetcites [105] Sharp KH Schneider S Cockayne A Paoli M Crystal structure of the heme-IsdC complex, the central conduit of the Isd iron/heme uptake system in Staphylococcus aureus J Biol Chem 282 2007 10625 10631 17287214 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“These NEAT-containing surface proteins (IsdB, IsdH, IsdA in S. aureus) shuttle heme to NEAT-containing IsdC.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Also, the Clp proteases have a role in Hb acquisition by modulating IsdB levels [121].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [121] Farrand AJ Reniere ML Ingmer H Frees D Skaar EP Regulation of host hemoglobin binding by the Staphylococcus aureus Clp proteolytic system J Bacteriol 195 2013 5041 5050 23995637 PMC3811588 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Isd-mediated heme acquisition is vital to the virulence of S. aureus.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [84] Skaar EP Humayun M Bae T DeBord KL Schneewind O Iron-source preference of Staphylococcus aureus infections Science 305 2004 1626 1628 15361626 source
- Not checked yetcites [85] Pishchany G Sheldon JR Dickson CF Alam MT Read TD Gell DA IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus J Infect Dis 209 2014 1764 1772 24338348 PMC4038968 source
- Not checked yetcites [86] Pishchany G McCoy AL Torres VJ Krause JC Crowe JE Jr Fabry ME Specificity for human hemoglobin enhances Staphylococcus aureus infection Cell Host Microbe 8 2010 544 550 21147468 PMC3032424 source
- Not checked yetcites [108] Torres VJ Pishchany G Humayun M Schneewind O Skaar EP Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization J Bacteriol 188 2006 8421 8429 17041042 PMC1698231 source
- Not checked yetcites [120] Reniere ML Skaar EP Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem Mol Microbiol 69 2008 1304 1315 18643935 PMC2597461 source
- Not checked yetcites [123] Visai L Yanagisawa N Josefsson E Tarkowski A Pezzali I Rooijakkers SH Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH Microbiology 155 2009 667 679 19246738 source
- Not checked yetcites [124] Cheng AG Kim HK Burts ML Krausz T Schneewind O Missiakas DM Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues FASEB J 23 2009 3393 3404 19525403 PMC2747682 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Isd proteins bind heme and Hb at the cell wall surface with conserved near transporter (NEAT) domains.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [104] Grigg JC Vermeiren CL Heinrichs DE Murphy ME Haem recognition by a Staphylococcus aureus NEAT domain Mol Microbiol 63 2007 139 149 17229211 source
- Not checked yetcites [105] Sharp KH Schneider S Cockayne A Paoli M Crystal structure of the heme-IsdC complex, the central conduit of the Isd iron/heme uptake system in Staphylococcus aureus J Biol Chem 282 2007 10625 10631 17287214 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During infection of iron-deplete niches, the heme acquisition system and associated iron-liberating heme oxygenases are expressed.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In addition to S. aureus and B. anthracis, many other pathogens have evolved NEAT-containing heme acquisition systems, including Staphylococcus lugdunensis, L. monocytogenes, and Streptococcus pyogenes [136–143].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [136] Farrand AJ Haley KP Lareau NM Heilbronner S McLean JA Foster T An iron-regulated autolysin remodels the cell wall to facilitate heme acquisition in Staphylococcus lugdunensis Infect Immun 83 2015 3578 3589 26123800 PMC4534641 source
- Not checked yetcites [137] Zapotoczna M Heilbronner S Speziale P Foster TJ Iron-regulated surface determinant (Isd) proteins of Staphylococcus lugdunensis J Bacteriol 194 2012 6453 6467 23002220 PMC3497513 source
- Not checked yetcites [138] Haley KP Janson EM Heilbronner S Foster TJ Skaar EP Staphylococcus lugdunensis IsdG liberates iron from host heme J Bacteriol 193 2011 4749 4757 21764939 PMC3165669 source
- Not checked yetcites [139] Malmirchegini GR Sjodt M Shnitkind S Sawaya MR Rosinski J Newton SM Novel mechanism of hemin capture by Hbp2, the hemoglobin-binding hemophore from Listeria monocytogenes J Biol Chem 289 2014 34886 34899 25315777 PMC4263887 source
- Not checked yetcites [140] Xiao Q Jiang X Moore KJ Shao Y Pi H Dubail I Sortase independent and dependent systems for acquisition of haem and haemoglobin in Listeria monocytogenes Mol Microbiol 80 2011 1581 1597 21545655 PMC3115469 source
- Not checked yetcites [141] Dahesh S Nizet V Cole JN Study of streptococcal hemoprotein receptor (Shr) in iron acquisition and virulence of M1T1 group A streptococcus Virulence 3 2012 566 575 23076332 PMC3545933 source
- Not checked yetcites [142] Ouattara M Cunha EB Li X Huang YS Dixon D Eichenbaum Z Shr of group A streptococcus is a new type of composite NEAT protein involved in sequestering haem from methaemoglobin Mol Microbiol 78 2010 739 756 20807204 PMC2963705 source
- Not checked yetcites [143] Ouattara M Pennati A Devlin DJ Huang YS Gadda G Eichenbaum Z Kinetics of heme transfer by the Shr NEAT domains of Group A Streptococcus Arch Biochem Biophys 538 2013 71 79 23993953 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“B. anthracis encodes two secreted hemophores termed IsdX1 and IsdX2 [125].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [125] Maresso AW Garufi G Schneewind O Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin PLoS Pathog 4 2008 e1000132 18725935 PMC2515342 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“IsdDEF transports heme across the membrane for utilization by IsdG, an orthologue of the S. aureus heme oxygenase [133].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [133] Skaar EP Gaspar AH Schneewind O Bacillus anthracis IsdG, a heme-degrading monooxygenase J Bacteriol 188 2006 1071 1080 16428411 PMC1347327 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The role of B. anthracis heme acquisition during infection is not clear.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Also, a mutant of B. anthracis lacking Hal demonstrated reduced virulence in a model of inhalational anthrax [135].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [135] Carlson PE Jr Carr KA Janes BK Anderson EC Hanna PC Transcriptional profiling of Bacillus anthracis Sterne (34F2) during iron starvation PLoS One 4 2009 e6988 19768119 PMC2742718 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Unlike IsdX1/2, Hal is sortase anchored to the cell wall [131].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [131] Gaspar AH Marraffini LA Glass EM Debord KL Ton-That H Schneewind O Bacillus anthracis sortase A (SrtA) anchors LPXTG motif-containing surface proteins to the cell wall envelope J Bacteriol 187 2005 4646 4655 15968076 PMC1151759 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“ChtAB and ChtC appear to be the result of gene duplication of HtaAB, as all three groups of proteins have sequence similarity, N-terminal secretion signals, and C-terminal transmembrane domains, and contain the same heme-binding domain [152].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [152] Allen CE Burgos JM Schmitt MP Analysis of novel iron-regulated, surface-anchored hemin-binding proteins in Corynebacterium diphtheriae J Bacteriol 195 2013 2852 2863 23585541 PMC3697262 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“This led to the characterization of the ChtAB and CirAChrC operons, which are regulated by iron levels via DtxR.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [150] Kunkle CA Schmitt MP Analysis of a DtxR-regulated iron transport and siderophore biosynthesis gene cluster in Corynebacterium diphtheriae J Bacteriol 187 2005 422 433 15629913 PMC543566 source
- Not checked yetcites [151] Kunkle CA Schmitt MP Analysis of the Corynebacterium diphtheriae DtxR regulon: identification of a putative siderophore synthesis and transport system that is similar to the Yersinia high-pathogenicity island-encoded yersiniabactin synthesis and uptake system J Bacteriol 185 2003 6826 6840 14617647 PMC262719 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Inactivation of the Hmu/Hta systems does not completely eliminate growth with heme as a sole iron source, suggesting the involvement of an additional heme uptake system [147].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [147] Allen CE Schmitt MP HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae J Bacteriol 191 2009 2638 2648 19201805 PMC2668399 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The Hmu (hemin-uptake) system was the first heme acquisition system described in Gram-positive organisms.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [144] Schmitt MP Utilization of host iron sources by Coryne-bacterium diphtheriae: identification of a gene whose product is homologous to eukaryotic heme oxygenases and is required for acquisition of iron from heme and hemoglobin J Bacteriol 179 1997 838 845 9006041 PMC178768 source
- Not checked yetcites [145] Drazek ES Hammack CA Schmitt MP Corynebacterium diphtheriae genes required for acquisition of iron from haemin and haemoglobin are homologous to ABC haemin transporters Mol Microbiol 36 2000 68 84 10760164 source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, a portion of HtaA is secreted and not anchored to the cell envelope.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [147] Allen CE Schmitt MP HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae J Bacteriol 191 2009 2638 2648 19201805 PMC2668399 source
- Not checked yetcites [148] Allen CE Schmitt MP Novel hemin binding domains in the Corynebacterium diphtheriae HtaA protein interact with hemoglobin and are critical for heme iron utilization by HtaA J Bacteriol 193 2011 5374 5385 21803991 PMC3187408 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“It was later discovered that an additional gene is encoded within the hmuTUV operon, termed htaA (heme-transport associated) [147].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [147] Allen CE Schmitt MP HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae J Bacteriol 191 2009 2638 2648 19201805 PMC2668399 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Sequence analysis suggests that HmuTUV acts asan ABC transporter that shuttles heme across the cell membrane [146].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [146] Thompson JM Jones HA Perry RD Molecular characterization of the hemin uptake locus (hmu) from Yersinia pestis and analysis of hmu mutants for hemin and hemoprotein utilization Infect Immun 67 1999 3879 3892 10417152 PMC96668 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The outer membrane of the cellular envelope of Gram-negative organisms presents an additional barrier to heme acquisition.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies
What the sources say
- Not checked yetcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The conservation of NEAT-mediated heme uptake highlights the contribution of host heme to bacterial infection.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Unlike the sortase anchoring of other Gram-positive uptake systems, HtaA and HtaB contain N-terminal secretion signals as well as C-terminal intermembrane domains.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [147] Allen CE Schmitt MP HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae J Bacteriol 191 2009 2638 2648 19201805 PMC2668399 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“The infections also selected for mutants that demonstrate enhanced expression of the feo ferrous-iron acquisition genes”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [166] Marvig RL Damkiaer S Khademi SM Markussen TM Molin S Jelsbak L Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin mBio 5 2014 e00966 14 24803516 PMC4010824 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“no biliverdin-β (the product of HemO heme catabolism) is detected in a mutant lacking hemO [164,165].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [164] Lee MJ Schep D McLaughlin B Kaufmann M Jia Z Structural analysis and identification of PhuS as a heme-degrading enzyme from Pseudomonas aeruginosa J Mol Biol 426 2014 1936 1946 24560694 source
- Not checked yetcites [165] O'Neill MJ Wilks A The P. aeruginosa heme binding protein PhuS is a heme oxygenase titratable regulator of heme uptake ACS Chem Biol 8 2013 1794 1802 23947366 PMC3748626 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“These clinical data confirm experimental findings suggesting that P. aeruginosa heme acquisition contributes to chronic infection.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [166] Marvig RL Damkiaer S Khademi SM Markussen TM Molin S Jelsbak L Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin mBio 5 2014 e00966 14 24803516 PMC4010824 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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In the paper
“suggesting that PhuS transfers heme to HemO specifically and not to the second Pseudomonas heme oxygense, BphO [160].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [160] Lansky IB Lukat-Rodgers GS Block D Rodgers KR Ratliff M Wilks A The cytoplasmic heme-binding protein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is an intracellular heme-trafficking protein to the delta-regioselective heme oxygenase J Biol Chem 281 2006 13652 13662 16533806 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“in vitro heme oxygenase activity has been attributed to PhuS”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [164] Lee MJ Schep D McLaughlin B Kaufmann M Jia Z Structural analysis and identification of PhuS as a heme-degrading enzyme from Pseudomonas aeruginosa J Mol Biol 426 2014 1936 1946 24560694 source
- Not checked yetcites [165] O'Neill MJ Wilks A The P. aeruginosa heme binding protein PhuS is a heme oxygenase titratable regulator of heme uptake ACS Chem Biol 8 2013 1794 1802 23947366 PMC3748626 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“suggest that heme is an important iron source during chronic Pseudomonas infection.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [166] Marvig RL Damkiaer S Khademi SM Markussen TM Molin S Jelsbak L Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin mBio 5 2014 e00966 14 24803516 PMC4010824 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“PhuS has been shown to bind heme as a monomer utilizing one of two histidine residues (His209 and His212)”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [161] Block DR Lukat-Rodgers GS Rodgers KR Wilks A Bhakta MN Lansky IB Identification of two heme-binding sites in the cytoplasmic heme-trafficking protein PhuS from Pseudomonas aeruginosa and their relevance to function Biochemistry 46 2007 14391 14402 18020455 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“PhuS, unlike many hemoproteins, binds ferric-iron heme and subsequently transfers it to HemOunder iron-deplete conditions [160].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [160] Lansky IB Lukat-Rodgers GS Block D Rodgers KR Ratliff M Wilks A The cytoplasmic heme-binding protein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is an intracellular heme-trafficking protein to the delta-regioselective heme oxygenase J Biol Chem 281 2006 13652 13662 16533806 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“It is capable of acquiring heme from diverse host sources (Fig. 3), including hemopexin, free heme, albumin-bound heme, myoglobin, and Hb”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [168] Stull TL Protein sources of heme for Haemophilus influenzae Infect Immun 55 1987 148 153 3025098 PMC260293 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the variety of heme sources is in accordance with its absolute reliance on exogenous heme [168].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [168] Stull TL Protein sources of heme for Haemophilus influenzae Infect Immun 55 1987 148 153 3025098 PMC260293 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This protein, PhuS, transfers heme to the heme-oxygenase HemO for iron liberation.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [160] Lansky IB Lukat-Rodgers GS Block D Rodgers KR Ratliff M Wilks A The cytoplasmic heme-binding protein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is an intracellular heme-trafficking protein to the delta-regioselective heme oxygenase J Biol Chem 281 2006 13652 13662 16533806 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These changes to phu transcription confer a growth advantage enabling the utilization of heme from Hb as the sole iron source”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [166] Marvig RL Damkiaer S Khademi SM Markussen TM Molin S Jelsbak L Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin mBio 5 2014 e00966 14 24803516 PMC4010824 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The dissociation constant of the heme–PhuS–HemO complex is in the nanomolar range”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [160] Lansky IB Lukat-Rodgers GS Block D Rodgers KR Ratliff M Wilks A The cytoplasmic heme-binding protein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is an intracellular heme-trafficking protein to the delta-regioselective heme oxygenase J Biol Chem 281 2006 13652 13662 16533806 source
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In the paper
“The P. aeruginosa heme uptake system PhuSTUV/PhuR is regulated by Fur in addition to the HasI sigma factor detailed above.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [157] Smith AD Wilks A Differential contributions of the outer membrane receptors PhuR and HasR to heme acquisition in Pseudomonas aeruginosa J Biol Chem 290 2015 7756 7766 25616666 PMC4367277 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and a third binding site exists when PhuS is in dimeric form [161].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [161] Block DR Lukat-Rodgers GS Rodgers KR Wilks A Bhakta MN Lansky IB Identification of two heme-binding sites in the cytoplasmic heme-trafficking protein PhuS from Pseudomonas aeruginosa and their relevance to function Biochemistry 46 2007 14391 14402 18020455 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Like other Gram-negative heme-binding motifs, HasA coordinates heme using histidine and tyrosine residues with picomolar affinity.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [155] Letoffe S Nato F Goldberg ME Wandersman C Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR Mol Microbiol 33 1999 546 555 10417645 source
- Not checked yetcites [156] Letoffe S Deniau C Wolff N Dassa E Delepelaire P Lecroisey A Haemophore-mediated bacterial haem transport: evidence for a common or overlapping site for haem-free and haem-loaded haemophore on its specific outer membrane receptor Mol Microbiol 41 2001 439 450 11489129 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“indicating that ferrous iron is also a source of bioavailable iron.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [166] Marvig RL Damkiaer S Khademi SM Markussen TM Molin S Jelsbak L Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin mBio 5 2014 e00966 14 24803516 PMC4010824 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“therefore requires heme uptake for aerobic respiration [167].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [167] Granick S Gilder H The porphyrin requirements of Haemophilus influenzae and some functions of the vinyl and propionic acid side chains of heme J Gen Physiol 30 1946 1 13 20997746 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Long-term infection led to the selection of mutations in the promoters of the phuSTUWV and phuR loci, resulting in greater Phu expression.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [166] Marvig RL Damkiaer S Khademi SM Markussen TM Molin S Jelsbak L Within-host evolution of Pseudomonas aeruginosa reveals adaptation toward iron acquisition from hemoglobin mBio 5 2014 e00966 14 24803516 PMC4010824 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“TonB is an inner-membrane protein with a substantial periplasmic portion for direct interaction with periplasmic domains of the outer membrane proteins.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, HasA/HasR (heme assimilation system) is utilized for heme uptake.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [155] Letoffe S Nato F Goldberg ME Wandersman C Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR Mol Microbiol 33 1999 546 555 10417645 source
- Not checked yetcites [156] Letoffe S Deniau C Wolff N Dassa E Delepelaire P Lecroisey A Haemophore-mediated bacterial haem transport: evidence for a common or overlapping site for haem-free and haem-loaded haemophore on its specific outer membrane receptor Mol Microbiol 41 2001 439 450 11489129 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is clear that for H. influenzae pathogenesis, heme uptake is a critical virulence determinant.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Animal models of H. influenzae infection reflect human pathogenesis.
None of the sources cited for this claim have been checked yet.
In the paper
“HxuA is a secreted hemophore that is released from the outer membrane by its transporter HxuB [169–171].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [169] Cope LD Thomas SE Hrkal Z Hansen EJ Binding of heme-hemopexin complexes by soluble HxuA protein allows utilization of this complexed heme by Haemophilus influenzae Infect Immun 66 1998 4511 4516 9712810 PMC108548 source
- Not checked yetcites [170] Cope LD Yogev R Muller-Eberhard U Hansen EJ A gene cluster involved in the utilization of both free heme and heme: hemopexin by Haemophilus influenzae type b J Bacteriol 177 1995 2644 2653 7751272 PMC176933 source
- Not checked yetcites [171] Baelen S Dewitte F Clantin B Villeret V Structure of the secretion domain of HxuA from Haemophilus influenzae Acta Crystallogr Sect F: Struct Biol Cryst Commun 69 2013 1322 1327 PMC3855712 24316822 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“consists of the HpuA lipoprotein and HpuB, the TonB-dependent receptor”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [190] Lewis LA Gray E Wang YP Roe BA Dyer DW Molecular characterization of hpuAB, the haemoglobin–hapto-globin-utilization operon of Neisseria meningitidis Mol Microbiol 23 1997 737 749 9157245 source
- Not checked yetcites [191] Lewis LA Dyer DW Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin J Bacteriol 177 1995 1299 1306 7868605 PMC176737 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Genetic evidence from clinical isolates suggests that heme uptake is vital to pathogenic strains of H. influenzae.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [186] Xie J Juliao PC Gilsdorf JR Ghosh D Patel M Marrs CF Identification of new genetic regions more prevalent in nontypeable Haemophilus influenzae otitis media strains than in throat strains J Clin Microbiol 44 2006 4316 4325 17005745 PMC1698427 source
- Not checked yetcites [187] Hariadi NI Zhang L Patel M Sandstedt SA Davis GS Marrs CF comparative profile of heme acquisition genes in disease-causing and colonizing nontypeable Haemophilus influenzae and Haemophilus haemolyticus J Clin Microbiol 53 2015 2132 2137 25903577 PMC4473220 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“the Hgp proteins are required to cause otitis media in a chinchilla model [189].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [189] Morton DJ Bakaletz LO Jurcisek JA VanWagoner TM Seale TW Whitby PW Reduced severity of middle ear infection caused by nontypeable Haemophilus influenzae lacking the hemoglobin/hemoglobin–haptoglobin binding proteins (Hgp) in a chinchilla model of otitis media Microb Pathog 36 2004 25 33 14643637 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Animal models of H. influenzae infection reflect human pathogenesis.
In the paper
“HxuC is capable of acquiring heme from serum albumin (Alb) independent of HxuA [174].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [174] Morton DJ Seale TW Madore LL VanWagoner TM Whitby PW Stull TL The haem-haemopexin utilization gene cluster (hxuCBA) as a virulence factor of Haemophilus influenzae Microbiology 153 2007 215 224 17185550 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“HpbA is another heme acquisition protein identified in nontypeable and type B H. influenzae.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [175] Morton DJ Madore LL Smith A Vanwagoner TM Seale TW Whitby PW The heme-binding lipoprotein (HbpA) of Haemophilus influenzae: role in heme utilization FEMS Microbiol Lett 253 2005 193 199 16289530 source
- Not checked yetcites [176] Morton DJ Seale TW Bakaletz LO Jurcisek JA Smith A VanWagoner TM The heme-binding protein (HbpA) of Haemophilus influenzae as a virulence determinant Int J Med Microbiol 299 2009 479 488 19451029 PMC2749905 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Upon heme transport into the cytoplasm, the HemO heme oxygenase degrades heme to biliverdin and liberates iron.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [192] Zhu W Wilks A Stojiljkovic I Degradation of heme in gram-negative bacteria: the product of the hemO gene of Neisseriae is a heme oxygenase J Bacteriol 182 2000 6783 6790 11073924 PMC111422 source
- Not checked yetcites [193] Zhu W Hunt DJ Richardson AR Stojiljkovic I Use of heme compounds as iron sources by pathogenic neisseriae requires the product of the hemO gene J Bacteriol 182 2000 439 447 10629191 PMC94294 source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“a heme oxygenase of Haemophilus has not been described”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“indicating that heme uptake may be a virulence determinant [186,187].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [186] Xie J Juliao PC Gilsdorf JR Ghosh D Patel M Marrs CF Identification of new genetic regions more prevalent in nontypeable Haemophilus influenzae otitis media strains than in throat strains J Clin Microbiol 44 2006 4316 4325 17005745 PMC1698427 source
- Not checked yetcites [187] Hariadi NI Zhang L Patel M Sandstedt SA Davis GS Marrs CF comparative profile of heme acquisition genes in disease-causing and colonizing nontypeable Haemophilus influenzae and Haemophilus haemolyticus J Clin Microbiol 53 2015 2132 2137 25903577 PMC4473220 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“HxuA exhibits no heme-binding motif”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [172] Fournier C Smith A Delepelaire P Haem release from haemopexin by HxuA allows Haemophilus influenzae to escape host nutritional immunity Mol Microbiol 80 2011 133 148 21276097 source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that acquired heme is utilized intact”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“other iron acquisition pathways, from transferrin and lactoferrin sources, are sufficient for cellular iron needs.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“A lipoprotein, HbpA is important for growth using Hb, Hp–Hb, and heme-human serum albumin as heme sources [175,176].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [175] Morton DJ Madore LL Smith A Vanwagoner TM Seale TW Whitby PW The heme-binding lipoprotein (HbpA) of Haemophilus influenzae: role in heme utilization FEMS Microbiol Lett 253 2005 193 199 16289530 source
- Not checked yetcites [176] Morton DJ Seale TW Bakaletz LO Jurcisek JA Smith A VanWagoner TM The heme-binding protein (HbpA) of Haemophilus influenzae as a virulence determinant Int J Med Microbiol 299 2009 479 488 19451029 PMC2749905 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“HpuB is sufficient to bind Hb”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [196] Chen CJ Elkins C Sparling PF Phase variation of hemoglobin utilization in Neisseria gonorrhoeae Infect Immun 66 1998 987 993 9488386 PMC108006 source
- Not checked yetcites [197] Rohde KH Dyer DW Analysis of haptoglobin and hemoglobin –haptoglobin interactions with the Neisseria meningitidis TonB-dependent receptor HpuAB by flow cytometry Infect Immun 72 2004 2494 2506 15102756 PMC387877 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In a model of H. influenzae bacteremia, infant rats infected with a mutant lacking HbpA completely clear the infection after one week while rats infected with wildtype remain infected [176].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [176] Morton DJ Seale TW Bakaletz LO Jurcisek JA Smith A VanWagoner TM The heme-binding protein (HbpA) of Haemophilus influenzae as a virulence determinant Int J Med Microbiol 299 2009 479 488 19451029 PMC2749905 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Animal models of H. influenzae infection reflect human pathogenesis.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“H. influenzae has evolved a variety of heme uptake systems important for growth in vitro using various host heme sources.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“HpuAB is expressed from an iron-repressed operon”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [190] Lewis LA Gray E Wang YP Roe BA Dyer DW Molecular characterization of hpuAB, the haemoglobin–hapto-globin-utilization operon of Neisseria meningitidis Mol Microbiol 23 1997 737 749 9157245 source
- Not checked yetcites [191] Lewis LA Dyer DW Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin J Bacteriol 177 1995 1299 1306 7868605 PMC176737 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“N. meningitidis encodes a bipartite heme uptake system consisting of HpuAB and HmbR (Fig. 3).”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [190] Lewis LA Gray E Wang YP Roe BA Dyer DW Molecular characterization of hpuAB, the haemoglobin–hapto-globin-utilization operon of Neisseria meningitidis Mol Microbiol 23 1997 737 749 9157245 source
- Not checked yetcites [191] Lewis LA Dyer DW Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin J Bacteriol 177 1995 1299 1306 7868605 PMC176737 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“a mutant lacking both HxuC and HgpABC uptake proteins is unable to cause bacteremia in the same rat model [188].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [188] Seale TW Morton DJ Whitby PW Wolf R Kosanke SD VanWagoner TM Complex role of hemoglobin and hemoglobin–haptoglobin binding proteins in Haemophilus influenzae virulence in the infant rat model of invasive infection Infect Immun 74 2006 6213 6225 16966415 PMC1695506 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Animal models of H. influenzae infection reflect human pathogenesis.
None of the sources cited for this claim have been checked yet.
In the paper
“H. influenzae encodes three receptors, HgpA, HgpB, and HgpC, that can acquire heme from Hp–Hb and Hp bound myoglobin, albeit it at greater concentrations than thought to be physiologically relevant [177,178].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [177] Morton DJ Van Wagoner TM Seale TW Whitby PW Stull TL Utilization of myoglobin as a heme source by Haemophilus influenzae requires binding of myoglobin to haptoglobin FEMS Microbiol Lett 258 2006 235 240 16640579 source
- Not checked yetcites [178] Morton DJ VanWagoner TM Seale TW Whitby PW Stull TL Differential utilization by Haemophilus influenzae of haemoglobin complexed to the three human haptoglobin phenotypes FEMS Immunol Med Microbiol 46 2006 426 432 16553817 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“hxuCBA and the hgp genes are expressed under in vitro iron/heme deplete conditions during experimental infection of the chinchilla ear [184,185].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [184] Whitby PW VanWagoner TM Seale TW Morton DJ Stull TL Comparison of transcription of the Haemophilus influenzae iron/heme modulon genes in vitro and in vivo in the chinchilla middle ear BMC Genomics 14 2013 925 24373462 PMC3879429 source
- Not checked yetcites [185] Whitby PW Seale TW VanWagoner TM Morton DJ Stull TL The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon BMC Genomics 10 2009 6 19128474 PMC2627913 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“HemO is required for survival using heme, Hb, or Hp–Hb as a sole iron source [192,193].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [192] Zhu W Wilks A Stojiljkovic I Degradation of heme in gram-negative bacteria: the product of the hemO gene of Neisseriae is a heme oxygenase J Bacteriol 182 2000 6783 6790 11073924 PMC111422 source
- Not checked yetcites [193] Zhu W Hunt DJ Richardson AR Stojiljkovic I Use of heme compounds as iron sources by pathogenic neisseriae requires the product of the hemO gene J Bacteriol 182 2000 439 447 10629191 PMC94294 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Hb can complement the deficiencies of a heme synthesis mutant in an HpuAB-dependent manner [194].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [194] Lewis LA Sung MH Gipson M Hartman K Dyer DW Transport of intact porphyrin by HpuAB, the hemoglobin– haptoglobin utilization system of Neisseria meningitidis J Bacteriol 180 1998 6043 6047 9811666 PMC107682 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Isolates from otitis media infection in children relative to commensal throat isolates exhibit greater rates of hxuA, hxuB, hxuC, and hgpB gene prevalence”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [186] Xie J Juliao PC Gilsdorf JR Ghosh D Patel M Marrs CF Identification of new genetic regions more prevalent in nontypeable Haemophilus influenzae otitis media strains than in throat strains J Clin Microbiol 44 2006 4316 4325 17005745 PMC1698427 source
- Not checked yetcites [187] Hariadi NI Zhang L Patel M Sandstedt SA Davis GS Marrs CF comparative profile of heme acquisition genes in disease-causing and colonizing nontypeable Haemophilus influenzae and Haemophilus haemolyticus J Clin Microbiol 53 2015 2132 2137 25903577 PMC4473220 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“HgpB has been demonstrated to be most important for utilization of Hp–Hb and Hp–myoglobin.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [177] Morton DJ Van Wagoner TM Seale TW Whitby PW Stull TL Utilization of myoglobin as a heme source by Haemophilus influenzae requires binding of myoglobin to haptoglobin FEMS Microbiol Lett 258 2006 235 240 16640579 source
- Not checked yetcites [178] Morton DJ VanWagoner TM Seale TW Whitby PW Stull TL Differential utilization by Haemophilus influenzae of haemoglobin complexed to the three human haptoglobin phenotypes FEMS Immunol Med Microbiol 46 2006 426 432 16553817 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“HmbR, based on spectroscopy and mutational analysis, also coordinates heme with a Tyr residue”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [203] Mokry DZ Nadia-Albete A Johnson MK Lukat-Rodgers GS Rodgers KR Lanzilotta WN Spectroscopic evidence for a 5-coordinate oxygenic ligated high spin ferric heme moiety in the Neisseria meningitidis hemoglobin binding receptor Biochim Biophys Acta 2014 1840 3058 3066 24968987 PMC4439194
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“HpuAB expression is equally associated with disease and carriage isolates”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [206] Harrison OB Evans NJ Blair JM Grimes HS Tinsley CR Nassif X Epidemiological evidence for the role of the hemoglobin receptor, MmbR, in meningococcal virulence J Infect Dis 200 2009 94 98 19476432 PMC2731217 source
- Not checked yetcites [207] Harrison OB Bennett JS Derrick JP Maiden MC Bayliss CD Distribution and diversity of the haemoglobin-haptoglobin iron-acquisition systems in pathogenic and non-pathogenic Neisseria Microbiology 159 2013 1920 1930 23813677 PMC3783016 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Most pathogenic isolates express at least HmbR”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [206] Harrison OB Evans NJ Blair JM Grimes HS Tinsley CR Nassif X Epidemiological evidence for the role of the hemoglobin receptor, MmbR, in meningococcal virulence J Infect Dis 200 2009 94 98 19476432 PMC2731217 source
- Not checked yetcites [207] Harrison OB Bennett JS Derrick JP Maiden MC Bayliss CD Distribution and diversity of the haemoglobin-haptoglobin iron-acquisition systems in pathogenic and non-pathogenic Neisseria Microbiology 159 2013 1920 1930 23813677 PMC3783016 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“N. meningitidis serotype B isolates associated with disease also exhibit “on” phase variation of HmbR”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [208] Lucidarme J Findlow J Chan H Feavers IM Gray SJ Kaczmarski EB The distribution and ‘in vivo’ phase variation status of haemoglobin receptors in invasive meningococcal serogroup B disease: genotypic and phenotypic analysis PLoS One 8 2013 e76932 24098814 PMC3786947 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“which suggests an additional layer of regulation for Hb acquisition.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [204] Sebastian S Agarwal S Murphy JR Genco CA The gonococcal Fur regulon: identification of additional genes involved in major catabolic, recombination, and secretory pathways J Bacteriol 184 2002 3965 3974 12081969 PMC135177 source
- Not checked yetcites [205] Zhao S Montanez GE Kumar P Sannigrahi S Tzeng YL Regulatory role of the MisR/S two-component system in hemoglobin utilization in Neisseria meningitidis Infect Immun 78 2010 1109 1122 20008531 PMC2825934 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“HpuA-Hb binding was not detected by a flow cytometry assay [196,197].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [196] Chen CJ Elkins C Sparling PF Phase variation of hemoglobin utilization in Neisseria gonorrhoeae Infect Immun 66 1998 987 993 9488386 PMC108006 source
- Not checked yetcites [197] Rohde KH Dyer DW Analysis of haptoglobin and hemoglobin –haptoglobin interactions with the Neisseria meningitidis TonB-dependent receptor HpuAB by flow cytometry Infect Immun 72 2004 2494 2506 15102756 PMC387877 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“MisRS activates the expression of hemO and hmbR independent of Hb and iron concentration”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [204] Sebastian S Agarwal S Murphy JR Genco CA The gonococcal Fur regulon: identification of additional genes involved in major catabolic, recombination, and secretory pathways J Bacteriol 184 2002 3965 3974 12081969 PMC135177 source
- Not checked yetcites [205] Zhao S Montanez GE Kumar P Sannigrahi S Tzeng YL Regulatory role of the MisR/S two-component system in hemoglobin utilization in Neisseria meningitidis Infect Immun 78 2010 1109 1122 20008531 PMC2825934 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“While not all N. meningitidis strains express both the HmbR and HpuAB systems, most express at least one.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [206] Harrison OB Evans NJ Blair JM Grimes HS Tinsley CR Nassif X Epidemiological evidence for the role of the hemoglobin receptor, MmbR, in meningococcal virulence J Infect Dis 200 2009 94 98 19476432 PMC2731217 source
- Not checked yetcites [207] Harrison OB Bennett JS Derrick JP Maiden MC Bayliss CD Distribution and diversity of the haemoglobin-haptoglobin iron-acquisition systems in pathogenic and non-pathogenic Neisseria Microbiology 159 2013 1920 1930 23813677 PMC3783016 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“which further confirms that diverse heme-binding domains have evolved to utilize tyrosine as the axial ligand [203].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [203] Mokry DZ Nadia-Albete A Johnson MK Lukat-Rodgers GS Rodgers KR Lanzilotta WN Spectroscopic evidence for a 5-coordinate oxygenic ligated high spin ferric heme moiety in the Neisseria meningitidis hemoglobin binding receptor Biochim Biophys Acta 2014 1840 3058 3066 24968987 PMC4439194
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“HmbR is required for virulence in an infant rat model of meningitis [200].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [200] Stojiljkovic I Hwa V de Saint Martin L O'Gaora P Nassif X Heffron F The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence Mol Microbiol 15 1995 531 541 7783623 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Animal models of N. meningitidis meningitis reflect human virulence.
In the paper
“correlating virulence with the expression of HmbR [208].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [208] Lucidarme J Findlow J Chan H Feavers IM Gray SJ Kaczmarski EB The distribution and ‘in vivo’ phase variation status of haemoglobin receptors in invasive meningococcal serogroup B disease: genotypic and phenotypic analysis PLoS One 8 2013 e76932 24098814 PMC3786947 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a co-crystal structure of Hb and an HpuA homolog from Kingella denitrificans has been solved [199].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [199] Wong CT Xu Y Gupta A Garnett JA Matthews SJ Hare SA Structural analysis of haemoglobin binding by HpuA from the Neisseriaceae family Nat Commun 6 2015 10172 26671256 PMC4703857 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Free heme is rapidly bactericidal toward various Gram-positive and Gram-negative pathogens in low- to mid-micromolar concentrations [33,222-225].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [33] Stauff DL Skaar EP Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection Mol Microbiol 72 2009 763 778 19400785 PMC2891670 source
- Not checked yetcites [222] Stauff DL Torres VJ Skaar EP Signaling and DNA-binding activities of the Staphylococcus aureus HssR–HssS two-component system required for heme sensing J Biol Chem 282 2007 26111 26121 17635909 source
- Not checked yetcites [223] Fernandez A Lechardeur D Derre-Bobillot A Couve E Gaudu P Gruss A Two coregulated efflux transporters modulate intracellular heme and protoporphyrin IX availability in Streptococcus agalactiae PLoS Pathog 6 2010 e1000860 20421944 PMC2858704 source
- Not checked yetcites [224] Rasmussen AW Alexander HL Perkins-Balding D Shafer WM Stojiljkovic I Resistance of Neisseria meningitidis to the toxic effects of heme iron and other hydrophobic agents requires expression of ght J Bacteriol 187 2005 5214 5223 16030215 PMC1196014 source
- Not checked yetcites [225] Wyckoff EE Lopreato GF Tipton KA Payne SM Shigella dysenteriae ShuS promotes utilization of heme as an iron source and protects against heme toxicity J Bacteriol 187 2005 5658 5664 16077111 PMC1196095 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In N. meningitidis, expression of hemO and hmbR is regulated by Fur as well as the MisRS TCS [204,205].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [204] Sebastian S Agarwal S Murphy JR Genco CA The gonococcal Fur regulon: identification of additional genes involved in major catabolic, recombination, and secretory pathways J Bacteriol 184 2002 3965 3974 12081969 PMC135177 source
- Not checked yetcites [205] Zhao S Montanez GE Kumar P Sannigrahi S Tzeng YL Regulatory role of the MisR/S two-component system in hemoglobin utilization in Neisseria meningitidis Infect Immun 78 2010 1109 1122 20008531 PMC2825934 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a recent structural characterization has described a direct, albeit weak, interaction between HpuA and Hb”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [199] Wong CT Xu Y Gupta A Garnett JA Matthews SJ Hare SA Structural analysis of haemoglobin binding by HpuA from the Neisseriaceae family Nat Commun 6 2015 10172 26671256 PMC4703857 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data implicate heme uptake, particularly HmbR, as an important component of Neisseria infection.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Animal models of N. meningitidis meningitis reflect human virulence.
None of the sources cited for this claim have been checked yet.
In the paper
“which indicates that HmbR is an indicator of pathogenesis [206,207].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [206] Harrison OB Evans NJ Blair JM Grimes HS Tinsley CR Nassif X Epidemiological evidence for the role of the hemoglobin receptor, MmbR, in meningococcal virulence J Infect Dis 200 2009 94 98 19476432 PMC2731217 source
- Not checked yetcites [207] Harrison OB Bennett JS Derrick JP Maiden MC Bayliss CD Distribution and diversity of the haemoglobin-haptoglobin iron-acquisition systems in pathogenic and non-pathogenic Neisseria Microbiology 159 2013 1920 1930 23813677 PMC3783016 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“iron can cycle between ferrous and ferric states via Fenton chemistry and the Haber-Weiss reaction (reaction 1), yielding a regenerating supply of ROS.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The Gram-negative N. gonorrhoeae encodes an efflux pump, MtrCDE, for hydrophobic molecules that is required for resistance to heme stress [239].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [239] Hagman KE Pan W Spratt BG Balthazar JT Judd RC Shafer WM Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system Microbiology 141 Pt 3 1995 611 622 7711899 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The toxicity of heme is likely the result of a combination of membrane disruption, membrane protein and lipid oxidation, and DNA damage.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“HrtAB is actively expressed during murine anthrax”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [33] Stauff DL Skaar EP Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection Mol Microbiol 72 2009 763 778 19400785 PMC2891670 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“porphyrins cause significant damage to bacterial DNA [232].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [232] Nir U Ladan H Malik Z Nitzan Y In vivo effects of porphyrins on bacterial DNA J Photochem Photobiol B 11 1991 295 306 1816365 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“bacteria must contend with heme damage and have evolved a variety of strategies to overcome heme toxicity (Fig. 4).”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Iron-mediated production of ROS can damage DNA, lipids, and proteins [226,227].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [226] Imlay JA Chin SM Linn S Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro Science 240 1988 640 642 2834821 source
- Not checked yetcites [227] Imlay JA Linn S DNA damage and oxygen radical toxicity Science 240 1988 1302 1309 3287616 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“heme is toxic in anaerobic conditions”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [229] Wakeman CA Stauff DL Zhang Y Skaar EP Differential activation of Staphylococcus aureus heme detoxification machinery by heme analogues J Bacteriol 196 2014 1335 1342 24443529 PMC3993332 source
- Not checked yetcites [230] Stojiljkovic I Kumar V Srinivasan N Non-iron metalloporphyrins: potent antibacterial compounds that exploit haem/Hb uptake systems of pathogenic bacteria Mol Microbiol 31 1999 429 442 10027961 source
- Not checked yetcites [231] Nitzan Y Wexler HM Finegold SM Inactivation of anaerobic bacteria by various photosensitized porphyrins or by hemin Curr Microbiol 29 1994 125 131 7765091 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“further implicating membrane damage as a component of heme stress [238].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [238] Mike LA Choby JE Brinkman PR Olive LQ Dutter BF Ivan SJ Two-component system cross-regulation integrates Bacillus anthracis response to heme and cell envelope stress PLoS Pathog 10 2014 e1004044 24675902 PMC3968170 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Heme efflux strategies have been primarily characterized in Gram-positive organisms”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Orthologues of HrtAB have been described in B. anthracis and Lactococcus lactis and are required for resistance to heme toxicity in these organisms [236].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [236] Lechardeur D Cesselin B Liebl U Vos MH Fernandez A Brun C Discovery of intracellular heme-binding protein HrtR, which controls heme efflux by the conserved HrtB–HrtA transporter in Lactococcus lactis J Biol Chem 287 2012 4752 4758 22084241 PMC3281666 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“hrtAB expression is activated by the HssRS heme sensing TCS [222,234,235].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [222] Stauff DL Torres VJ Skaar EP Signaling and DNA-binding activities of the Staphylococcus aureus HssR–HssS two-component system required for heme sensing J Biol Chem 282 2007 26111 26121 17635909 source
- Not checked yetcites [234] Stauff DL Bagaley D Torres VJ Joyce R Anderson KL Kuechenmeister L Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response J Bacteriol 190 2008 3588 3596 18326576 PMC2395006 source
- Not checked yetcites [235] Torres VJ Stauff DL Pishchany G Bezbradica JS Gordy LE Iturregui J A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence Cell Host Microbe 1 2007 109 119 18005689 PMC2083280 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“suggesting that organisms that replicate in the bloodstream must tolerate heme toxicity [33].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [33] Stauff DL Skaar EP Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection Mol Microbiol 72 2009 763 778 19400785 PMC2891670 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the heme oxygenase outlined as part of heme acquisition strategies may contribute to the reduction of heme toxicity by cleaving the porphyrin ring and liberating iron for use.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These systems consist primarily of efflux and sequestration.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Three systems have been described, HrtAB, PefAB/CD, and MtrCDE.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Further evidence suggests that iron-mediated ROS production and subsequent membrane damage are an insufficient description of heme toxicity.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, iron itself may be liberated from the porphyrin ring upon reaction with reactive oxygen species (ROS).”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“resistance to heme toxicity is in part mediated in N. meningitidis by Ght (gene of hydrophobic agent tolerance)”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [224] Rasmussen AW Alexander HL Perkins-Balding D Shafer WM Stojiljkovic I Resistance of Neisseria meningitidis to the toxic effects of heme iron and other hydrophobic agents requires expression of ght J Bacteriol 187 2005 5214 5223 16030215 PMC1196014 source
- Not checked yetcites [233] Putker F Grutsch A Tommassen J Bos MP Ght protein of Neisseria meningitidis is involved in the regulation of lipopoly-saccharide biosynthesis J Bacteriol 196 2014 780 789 24296673 PMC3911185 source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“First, a portion of iron is freed by the heme oxygenases.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“excess exogenous or endogenous heme leads to activation, either directly or indirectly [99].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [99] Mike LA Dutter BF Stauff DL Moore JL Vitko NP Aranmolate O Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus Proc Natl Acad Sci USA 110 2013 9206 8211 PMC3657828 23630262 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“HrtA is an ATPase that drives efflux by HrtB permease of its ligand, likely heme.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“When the Hrt efflux pump is inactivated in both S. aureus and L. lactis, levels of intracellular heme increase”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [229] Wakeman CA Stauff DL Zhang Y Skaar EP Differential activation of Staphylococcus aureus heme detoxification machinery by heme analogues J Bacteriol 196 2014 1335 1342 24443529 PMC3993332 source
- Not checked yetcites [237] Joubert L Derre-Bobillot A Gaudu P Gruss A Lechardeur D HrtBA and menaquinones control haem homeostasis in Lactococcus lactis Mol Microbiol 93 2014 823 833 25040434 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“suggesting that heme is the substrate of HrtAB export [229,237].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [229] Wakeman CA Stauff DL Zhang Y Skaar EP Differential activation of Staphylococcus aureus heme detoxification machinery by heme analogues J Bacteriol 196 2014 1335 1342 24443529 PMC3993332 source
- Not checked yetcites [237] Joubert L Derre-Bobillot A Gaudu P Gruss A Lechardeur D HrtBA and menaquinones control haem homeostasis in Lactococcus lactis Mol Microbiol 93 2014 823 833 25040434 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The S. aureus heme-regulated transporter HrtAB is required for survival in toxic concentrations of heme.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [222] Stauff DL Torres VJ Skaar EP Signaling and DNA-binding activities of the Staphylococcus aureus HssR–HssS two-component system required for heme sensing J Biol Chem 282 2007 26111 26121 17635909 source
- Not checked yetcites [234] Stauff DL Bagaley D Torres VJ Joyce R Anderson KL Kuechenmeister L Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response J Bacteriol 190 2008 3588 3596 18326576 PMC2395006 source
- Not checked yetcites [235] Torres VJ Stauff DL Pishchany G Bezbradica JS Gordy LE Iturregui J A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence Cell Host Microbe 1 2007 109 119 18005689 PMC2083280 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“investigation of heme toxicity in a variety of bacterial species has led to a model of heme inducing iron- and non-iron-related damage to the cell.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [26] Anzaldi LL Skaar EP Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens Infect Immun 78 2010 4977 4989 20679437 PMC2981329 source
- Not checked yetcites [221] Van Heyningen WE Inhibition of aerobic sporing bacilli by haematin Nature 162 1948 114 18939229 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“non-HemS family proteins have been found to bind heme and play a role in heme homeostasis, including the small outer-membrane Protein E of H. influenzae and the Cu,Zn superoxide dismutase of Haemophilus ducreyi [245,246].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [245] Al Jubair T Singh B Fleury C Blom AM Morgelin M Thunnissen MM Haemophilus influenzae stores and distributes hemin by using protein E Int J Med Microbiol 304 2014 662 668 24863527 source
- Not checked yetcites [246] Negari S Sulpher J Pacello F Ingrey K Battistoni A Lee BC A role for Haemophilus ducreyi Cu, ZnSOD in resistance to heme toxicity Biometals 21 2008 249 258 17704897 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“transgenic mice expressing human Hb are more susceptible to S. aureus disease [86].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > Current challenges and opportunities
What the sources say
- Not checked yetcites [86] Pishchany G McCoy AL Torres VJ Krause JC Crowe JE Jr Fabry ME Specificity for human hemoglobin enhances Staphylococcus aureus infection Cell Host Microbe 8 2010 544 550 21147468 PMC3032424 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“ChuS, which also has heme oxygenase activity”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [240] Stojiljkovic I Hantke K Transport of haemin across the cytoplasmic membrane through a haemin-specific periplasmic binding-protein-dependent transport system in Yersinia enter-ocolitica Mol Microbiol 13 1994 719 732 7997183 source
- Not checked yetcites [241] Suits MD Pal GP Nakatsu K Matte A Cygler M Jia Z Identification of an Escherichia coli O157:H7 heme oxygenase with tandem functional repeats Proc Natl Acad Sci USA 102 2005 16955 16960 16275907 PMC1287972 source
- Not checked yetcites [242] Ouellet YH Ndiaye CT Gagne SM Sebilo A Suits MD Jubinville E An alternative reaction for heme degradation catalyzed by the Escherichia coli O157:H7 ChuS protein: release of hematinic acid, tripyrrole and Fe(III) J Inorg Biochem 154 2016 103 113 26598215 source
- Not checked yetcites [243] Kaur AP Lansky IB Wilks A The role of the cytoplasmic heme-binding protein (PhuS) of Pseudomonas aeruginosa in intracellular heme trafficking and iron homeostasis J Biol Chem 284 2009 56 66 18990702 PMC2610525 source
- Not checked yetcites [244] Kaur AP Wilks A Heme inhibits the DNA binding properties of the cytoplasmic heme binding protein of Shigella dysenteriae (ShuS) Biochemistry 46 2007 2994 3000 17323920 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The conserved HemS family has been described in Yersinia enterocolitica, Y. pestis, Shigella dysenteriae (termed ShuS), P. aeruginosa (called PhuS, detailed above), and E. coli (ChuS, which also has heme oxygenase activity) [146,160,225,240–244].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [146] Thompson JM Jones HA Perry RD Molecular characterization of the hemin uptake locus (hmu) from Yersinia pestis and analysis of hmu mutants for hemin and hemoprotein utilization Infect Immun 67 1999 3879 3892 10417152 PMC96668 source
- Not checked yetcites [160] Lansky IB Lukat-Rodgers GS Block D Rodgers KR Ratliff M Wilks A The cytoplasmic heme-binding protein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is an intracellular heme-trafficking protein to the delta-regioselective heme oxygenase J Biol Chem 281 2006 13652 13662 16533806 source
- Not checked yetcites [225] Wyckoff EE Lopreato GF Tipton KA Payne SM Shigella dysenteriae ShuS promotes utilization of heme as an iron source and protects against heme toxicity J Bacteriol 187 2005 5658 5664 16077111 PMC1196095 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heme sequestration and storage is a second theme in strategies to resist heme toxicity.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“suggesting that the co-evolution of humans and pathogens has produced an evolutionary arms race in the context of nutritional immunity [217,218].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > Current challenges and opportunities
What the sources say
- Not checked yetcites [217] Barber MF Elde NC Nutritional immunity. Escape from bacterial iron piracy through rapid evolution of transferrin Science 346 2014 1362 1366 25504720 PMC4455941 source
- Not checked yetcites [218] Barber MF Elde NC Buried treasure: evolutionary perspectives on microbial iron piracy Trends Genet 31 2015 627 636 26431675 PMC4639441 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“the human and primate iron-binding protein transferrin has undergone positive selection at the interface of binding by bacterial transferrin receptors”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > Current challenges and opportunities
What the sources say
- Not checked yetcites [217] Barber MF Elde NC Nutritional immunity. Escape from bacterial iron piracy through rapid evolution of transferrin Science 346 2014 1362 1366 25504720 PMC4455941 source
- Not checked yetcites [218] Barber MF Elde NC Buried treasure: evolutionary perspectives on microbial iron piracy Trends Genet 31 2015 627 636 26431675 PMC4639441 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 114
- Probably not a substantial claim. 33
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Upon PhuR translocation of heme into the periplasm, the soluble periplasmic protein PhuT binds heme and brings it to PhuUV, an ABC transporter at the inner membrane.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Partly supportedcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 sourceExperimental — accuracy not yet measured
The Introduction (page not available) describes transport across the outer membrane into the periplasm before inner-membrane translocation. It does not identify PhuR, PhuT, or PhuUV, or describe PhuT binding heme and delivering it to PhuUV; searches for those names and the heme-transfer pathway found no supporting passage. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“Heme, a porphyrin ring complexed with iron, serves as a redox active moiety required for the function of many cellular proteins.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
What the sources say
- Not checked yetcites [1] Chen JJ London IM Hemin enhances the differentiation of mouse 3T3 cells to adipocytes Cell 26 1981 117 122 6799206 source
- Not checked yetcites [2] Shelver D Kerby RL He Y Roberts GP CooA, a CO-sensing transcription factor from Rhodospirillum rubrum, is a CO-binding heme protein Proc Natl Acad Sci USA 94 1997 11216 11220 9326589 PMC23420 source
- Not checked yetcites [3] Faller M Matsunaga M Yin S Loo JA Guo F Heme is involved in microRNA processing Nat Struct Mol Biol 14 2007 23 29 17159994 source
- Not checked yetcites [4] Bonyhady RE Hendry IA Hill CE McLennan IS Effects of haemin on neurones derived from the neural crest Dev Neurosci 5 1982 125 129 6127199 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“iron can act alone or in iron–sulfur clusters as a prosthetic moiety for members of the oxidoreductase, nitrogenase, hydrogenase, dehydrogenase, and hydratase enzyme families [7–12].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
What the sources say
- Not checked yetcites [7] Kessler D Leibrecht I Knappe J Pyruvate-formate-lyasedeactivase and acetyl-CoA reductase activities of Escherichia coli reside on a polymeric protein particle encoded by adhE FEBS Lett 281 1991 59 63 2015910 source
- Not checked yetcites [8] Yamamoto I Saiki T Liu SM Ljungdahl LG Purification and properties of NADP-dependent formate dehydrogenase from Clostridium thermoaceticum, a tungsten–selenium–iron protein J Biol Chem 258 1983 1826 1832 6822536 source
- Not checked yetcites [9] Peters JW Lanzilotta WN Lemon BJ Seefeldt LC X-ray crystal structure of the Fe-only hydrogenase (CpI) from Clostridium pasteurianum to 1.8 Angstrom resolution Science 282 1998 1853 1858 9836629 source
- Not checked yetcites [10] Nagashima S Nakasako M Dohmae N Tsujimura M Takio K Odaka M Novel non-heme iron center of nitrile hydratase with a claw setting of oxygen atoms Nat Struct Biol 5 1998 347 351 9586994 source
- Not checked yetcites [11] Johnson DC Dean DR Smith AD Johnson MK Structure, function, and formation of biological iron–sulfur clusters Annu Rev Biochem 74 2005 247 281 15952888 source
- Not checked yetcites [12] Shomura Y Yoon KS Nishihara H Higuchi Y Structural basis for a [4Fe–3S] cluster in the oxygen-tolerant membrane-bound [NiFe]-hydrogenase Nature 479 2011 253 256 22002607 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“both heme acquisition and synthesis are important for pathogenesis”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Heme functions as an electron shuttle in enzymes of the electron transport chain and is required for cellular respiration.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
What the sources say
- Not checked yetcites [22] Rieske JS Composition, structure and function of complex III of the respiratory chain Biochim Biophys Acta 456 1976 195 247 788795 source
- Not checked yetcites [23] Omura T Sato R The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature J Biol Chem 239 1964 2370 2378 14209971 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, nearly all organisms must satisfy the requirement for heme through either synthesis or acquisition.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Heme is also an important molecule involved in diverse cellular processes including signaling, gas sensing, microRNA processing, and cellular differentiation [1–4].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
What the sources say
- Not checked yetcites [1] Chen JJ London IM Hemin enhances the differentiation of mouse 3T3 cells to adipocytes Cell 26 1981 117 122 6799206 source
- Not checked yetcites [2] Shelver D Kerby RL He Y Roberts GP CooA, a CO-sensing transcription factor from Rhodospirillum rubrum, is a CO-binding heme protein Proc Natl Acad Sci USA 94 1997 11216 11220 9326589 PMC23420 source
- Not checked yetcites [3] Faller M Matsunaga M Yin S Loo JA Guo F Heme is involved in microRNA processing Nat Struct Mol Biol 14 2007 23 29 17159994 source
- Not checked yetcites [4] Bonyhady RE Hendry IA Hill CE McLennan IS Effects of haemin on neurones derived from the neural crest Dev Neurosci 5 1982 125 129 6127199 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The tetrapyrrole cofactor heme is important for the cellular processes of most organisms and essential to many lifeforms across domains of life.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
What the sources say
- Not checked yetcites [1] Chen JJ London IM Hemin enhances the differentiation of mouse 3T3 cells to adipocytes Cell 26 1981 117 122 6799206 source
- Not checked yetcites [2] Shelver D Kerby RL He Y Roberts GP CooA, a CO-sensing transcription factor from Rhodospirillum rubrum, is a CO-binding heme protein Proc Natl Acad Sci USA 94 1997 11216 11220 9326589 PMC23420 source
- Not checked yetcites [3] Faller M Matsunaga M Yin S Loo JA Guo F Heme is involved in microRNA processing Nat Struct Mol Biol 14 2007 23 29 17159994 source
- Not checked yetcites [4] Bonyhady RE Hendry IA Hill CE McLennan IS Effects of haemin on neurones derived from the neural crest Dev Neurosci 5 1982 125 129 6127199 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Like heme, iron is nearly universally required for life, and only a few exceptions have been identified [5,6].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Iron-binding proteins function to transport iron, protect host cells from iron-mediated oxidative damage, and keep iron from pathogens.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“bacterial pathogens have developed exquisite tactics to overcome iron limitation and elaborate high-affinity iron receptors and chelators”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In serum, heme is immediately bound by the highly abundant albumin (kd ≈ 10 nM) then transferred to hemopexin (kd < 1 pM) [30].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [30] Tolosano E Altruda F Hemopexin: structure, function, and regulation DNA Cell Biol 21 2002 297 306 12042069 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Humans and other metazoa synthesize heme through a variety of steps in the mitochondria and cytosol. This pathway, called the Shemin or four-carbon pathway, begins with the condensation of glycine and succinyl-CoA to form the committed precursor δ-aminolevulinic acid (ALA) [19–21].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [19] Wriston JC Jr Lack L Shemin D The mechanism of porphyrin formation; further evidence on the relationship of the citric acid cycle and porphyrin formation J Biol Chem 215 1955 603 611 13242557 source
- Not checked yetcites [20] Kikuchi G Shemin D Bachmann BJ The enzymic synthesis of delta-aminolevulinic acid Biochim Biophys Acta 28 1958 219 220 13535711 source
- Not checked yetcites [21] Hamza I Dailey HA One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans Biochim Biophys Acta 2012 1823 1617 1632 PMC3412874 22575458
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The heme is delivered to cells expressing the hemopexin receptor; these cells then degrade the heme using heme oxygenases [30].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [30] Tolosano E Altruda F Hemopexin: structure, function, and regulation DNA Cell Biol 21 2002 297 306 12042069 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A series of enzymes produces protoporphyrin IX from ALA and iron is inserted, forming protoheme IX.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [19] Wriston JC Jr Lack L Shemin D The mechanism of porphyrin formation; further evidence on the relationship of the citric acid cycle and porphyrin formation J Biol Chem 215 1955 603 611 13242557 source
- Not checked yetcites [20] Kikuchi G Shemin D Bachmann BJ The enzymic synthesis of delta-aminolevulinic acid Biochim Biophys Acta 28 1958 219 220 13535711 source
- Not checked yetcites [21] Hamza I Dailey HA One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans Biochim Biophys Acta 2012 1823 1617 1632 PMC3412874 22575458
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hb contains about two-thirds of the body's iron, and a single erythrocyte contains more than 280 million molecules of Hb [15,24].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
- Not checked yetcites [24] Bridges KR Seligman PA Disorders of Iron Metabolism J.B Lippincott Company New York 1995
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nutritional immunity has since been expanded to include the host processes that manipulate local levels of manganese, zinc, and other transition metals in order to metal starve or intoxicate the invading pathogens”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
- Not checked yetcites [16] Hood MI Skaar EP Nutritional immunity: transition metals at the pathogen-host interface Nat Rev Microbiol 10 2012 525 537 22796883 PMC3875331 source
- Not checked yetcites [17] Zackular JP Chazin WJ Skaar EP Nutritional immunity: S100 proteins at the host–pathogen interface J Biol Chem 290 2015 18991 18998 26055713 PMC4521021 source
- Not checked yetcites [18] Juttukonda LJ Skaar EP Manganese homeostasis and utilization in pathogenic bacteria Mol Microbiol 97 2015 216 228 25898914 PMC4631260 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Hemoproteins involved in tissue oxygen homeostasis include myoglobin and neuroglobin.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [22] Rieske JS Composition, structure and function of complex III of the respiratory chain Biochim Biophys Acta 456 1976 195 247 788795 source
- Not checked yetcites [23] Omura T Sato R The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature J Biol Chem 239 1964 2370 2378 14209971 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Energy generation by the electron transport chain relies on heme-dependent c- and b-type cytochromes of the ubiquinol–ferricytochrome c oxidoreductase (Complex III) family [22,23].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [22] Rieske JS Composition, structure and function of complex III of the respiratory chain Biochim Biophys Acta 456 1976 195 247 788795 source
- Not checked yetcites [23] Omura T Sato R The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature J Biol Chem 239 1964 2370 2378 14209971 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The abundance of cell-free Hb is thought to be very low in healthy adults, but a variety of genetic disorders, infections, and other disease states can increase the concentration of free Hb [28].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [28] Schaer DJ Buehler PW Cell-free hemoglobin and its scavenger proteins: new disease models leading the way to targeted therapies Cold Spring Harb Perspect Med 3 2013 PMC3662353 23645855 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, organisms have evolved elaborate strategies to acquire, store, and regulate intracellular iron for heme-dependent and other iron-dependent enzymes.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme and iron are essential for life
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The limited access of pathogens to metals serves as an antimicrobial strategy and limits bacterial replication.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
- Not checked yetcites [16] Hood MI Skaar EP Nutritional immunity: transition metals at the pathogen-host interface Nat Rev Microbiol 10 2012 525 537 22796883 PMC3875331 source
- Not checked yetcites [17] Zackular JP Chazin WJ Skaar EP Nutritional immunity: S100 proteins at the host–pathogen interface J Biol Chem 290 2015 18991 18998 26055713 PMC4521021 source
- Not checked yetcites [18] Juttukonda LJ Skaar EP Manganese homeostasis and utilization in pathogenic bacteria Mol Microbiol 97 2015 216 228 25898914 PMC4631260 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nutritional immunity, a concept articulated primarily by Eugene Weinberg in the 1970s, describes the processes by which humans and other organisms sequester iron to limit acquisition by bacterial pathogens [13,14].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Nutritional immunity limits host iron availability
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Heme makes up the greatest reservoir of iron in the host and serves as an iron source for many bacterial pathogens.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [15] Cassat JE Skaar EP Iron in infection and immunity Cell Host Microbe 13 2013 509 519 23684303 PMC3676888 source
- Not checked yetcites [24] Bridges KR Seligman PA Disorders of Iron Metabolism J.B Lippincott Company New York 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Heme is then bound by hemoproteins to serve a variety of intracellular and extracellular tasks.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [22] Rieske JS Composition, structure and function of complex III of the respiratory chain Biochim Biophys Acta 456 1976 195 247 788795 source
- Not checked yetcites [23] Omura T Sato R The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature J Biol Chem 239 1964 2370 2378 14209971 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“To prevent excess heme toxicity, eukaryotic heme synthesis is highly regulated and heme homeostasis and sequestration are well orchestrated.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [25] Everse J Hsia N The toxicities of native and modified hemoglobins Free Radic Biol Med 22 1997 1075 1099 9034247 source
- Not checked yetcites [26] Anzaldi LL Skaar EP Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens Infect Immun 78 2010 4977 4989 20679437 PMC2981329 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Catalase, peroxidase, and myeloperoxidase rely on heme to catalyze the hydrolysis of peroxide molecules.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [22] Rieske JS Composition, structure and function of complex III of the respiratory chain Biochim Biophys Acta 456 1976 195 247 788795 source
- Not checked yetcites [23] Omura T Sato R The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature J Biol Chem 239 1964 2370 2378 14209971 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The gluta-myl-tRNA reductase HemA produces the highly reactive intermediate glutamate-1-semialdehyde, which HemL, a glutamate-1-semialdehyde amino-mutase, converts to ALA [36,37].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [36] Hoober JK Kahn A Ash DE Gough S Kannangara CG Biosynthesis of delta-aminolevulinate in greening barley leaves. IX. Structure of the substrate, mode of gabaculine inhibition, and the catalytic mechanism of glutamate 1-semialdehyde aminotransferase Carlsb Res Commun 53 1988 3256306 source
- Not checked yetcites [37] Kannangara CG Gough SP Bruyant P Hoober JK Kahn A von Wettstein D tRNA(Glu) as a cofactor in delta-aminolevulinate biosynthesis: steps that regulate chlorophyll synthesis Trends Biochem Sci 13 1988 139 143 3075378 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“HemG, in Gammaproteobacteria and some Alphaproteobactera and Deltaproteobacteria, uses the respiratory chain as its electron acceptor and is not dependent on oxygen [48].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [48] Boynton TO Daugherty LE Dailey TA Dailey HA Identification of Escherichia coli HemG as a novel, menadione-dependent flavodoxin with protoporphyrinogen oxidase activity Biochemistry 48 2009 6705 6711 19583219 PMC2749469 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The addition of heme to cell extracts of E. coli reduces total HemA activity, without inhibiting the activity of the purified enzyme [58,59].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [58] Jahn D Michelsen U Soll D Two glutamyl-tRNA reductase activities in Escherichia coli J Biol Chem 266 1991 2542 2548 1990004 source
- Not checked yetcites [59] Javor GT Febre EF Enzymatic basis of thiol-stimulated secretion of porphyrins by Escherichia coli J Bacteriol 174 1992 1072 1075 1732201 PMC206203 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The three steps, from ALA to uroporphyrinogen, are well conserved and thought to be the evolutionary core of heme biosynthesis.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [38] Hansson M Rutberg L Schroder I Hederstedt L The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes of the biosynthetic pathway from glutamate to uroporphyrinogen III J Bacteriol 173 1991 2590 2599 1672867 PMC207825 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Very few HemF or HemN coproporphyrinogen oxidases can be identified in Gram-positive genomes; instead it has been realized that the annotated HemY in these organisms functions as a coproporphyrinogen oxidase to form coproporphyrin III [34,53].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [34] Dailey HA Gerdes S Dailey TA Burch JS Phillips JD Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin Proc Natl Acad Sci USA 112 2015 2210 2215 25646457 PMC4343137 source
- Not checked yetcites [53] Hansson M Gustafsson MC Kannangara CG Hederstedt L Isolated Bacillus subtilis HemY has copropor-phyrinogen III to coproporphyrin III oxidase activity Biochim Biophys Acta 1340 1997 97 104 9217019 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Regulation of HemA is typically heme-dependent, indicating that bacteria reduce synthesis of heme and all intermediates in heme-replete conditions.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“During infection of host heme- and Hb-replete niches, bacterial pathogens experience heme toxicity and encode systems to protect from heme toxicity as well [33].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Introduction > Heme is an important host iron source
What the sources say
- Not checked yetcites [33] Stauff DL Skaar EP Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection Mol Microbiol 72 2009 763 778 19400785 PMC2891670 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Uroporphyrinogen III can be utilized for the synthesis of several tetrapyrrole-based cofactors.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [42] Hansson M Hederstedt L Cloning and characterization of the Bacillus subtilis hemEHY gene cluster, which encodes protoheme IX biosynthetic enzymes J Bacteriol 174 1992 8081 8093 1459957 PMC207547 source
- Not checked yetcites [43] Leeper FJ The biosynthesis of porphyrins, chlorophylls, and vitamin B12 Nat Prod Rep 4 1987 441 469 3325863 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Uroporphyrinogen III decarboxylase (HemE) decarboxylates the four acetate side chains to methyl groups, producing coproporphyrinogen III, the next step in heme synthesis [42].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [42] Hansson M Hederstedt L Cloning and characterization of the Bacillus subtilis hemEHY gene cluster, which encodes protoheme IX biosynthetic enzymes J Bacteriol 174 1992 8081 8093 1459957 PMC207547 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“HemJ is poorly characterized but represents the most common protoporphyrinogen oxidase among Alphaproteobactera and Deltaproteobacteria [49].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [49] Kobayashi K Masuda T Tajima N Wada H Sato N Molecular phylogeny and intricate evolutionary history of the three isofunctional enzymes involved in the oxidation of protoporphyrinogen IX Genome Biol Evol 6 2014 2141 2155 25108393 PMC4231631 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The contribution of the Ahb alternative heme pathway has not been demonstrated in bacterial pathogens.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The Ahb enzymes of some archaea and sulfur-reducing bacteria can convert siroheme (produced from uroporphyrinogen) to heme [44,45].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [44] Bali S Lawrence AD Lobo SA Saraiva LM Golding BT Palmer DJ Molecular hijacking of siroheme for the synthesis of heme and d1 heme Proc Natl Acad Sci USA 108 2011 18260 18265 21969545 PMC3215036 source
- Not checked yetcites [45] Bali S Palmer DJ Schroeder S Ferguson SJ Warren MJ Recent advances in the biosynthesis of modified tetrapyrroles: the discovery of an alternative pathway for the formation of heme and heme d 1 Cell Mol Life Sci 71 2014 2837 2863 24515122 PMC11113276 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Additionally, uroporphyrinogen III can be shunted from heme synthesis and converted to precorrin-2 to synthesize vitamin B12, coenzyme F430, and siroheme [43].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [43] Leeper FJ The biosynthesis of porphyrins, chlorophylls, and vitamin B12 Nat Prod Rep 4 1987 441 469 3325863 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The terminal steps of the classical pathway were considered universally conserved for all heme synthesizing organisms.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Divergent heme synthesis pathways in Gramnegative and Gram-positive organisms
What the sources say
- Not checked yetcites [34] Dailey HA Gerdes S Dailey TA Burch JS Phillips JD Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin Proc Natl Acad Sci USA 112 2015 2210 2215 25646457 PMC4343137 source
- Not checked yetcites [52] Lobo SA Scott A Videira MA Winpenny D Gardner M Palmer MJ Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway Mol Microbiol 97 2015 472 487 25908396 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Similarly, Pseudomonas hemF and hemN are expressed anaerobically under the control of Anr and Dnr, while Anr induces the expression of only hemN aerobically [79].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [79] Rompf A Hungerer C Hoffmann T Lindenmeyer M Romling U Gross U Regulation of Pseudomonas aeruginosa hemF and hemN by the dual action of the redox response regulators Anr and Dnr Mol Microbiol 29 1998 985 997 9767567 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“As in B. subtilis, PerR has been implicated as a regulator of the hemEHY operon in Staphylococcus aureus; yet recent work has demonstrated that major differences exist between B. subtilis and S. aureus PerR orthologs, and therefore, it is difficult to conclude that PerR plays a role in S. aureus heme synthesis [69,70].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [69] Ji CJ Kim JH Won YB Lee YE Choi TW Ju SY Staphylococcus aureus PerR Is a hypersensitive hydrogen peroxide sensor using iron-mediated histidine oxidation J Biol Chem 290 2015 20374 20386 26134568 PMC4536443 source
- Not checked yetcites [70] Ravcheev DA Best AA Tintle N Dejongh M Osterman AL Novichkov PS Inference of the transcriptional regulatory network in Staphylococcus aureus by integration of experimental and genomics-based evidence J Bacteriol 193 2011 3228 3240 21531804 PMC3133287 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, mutations in HemA have been described that render HemA resistant to heme- and protease-mediated degradation, indicating that HemA binds excess heme, and holo-HemA but not apo-HemA is a substrate for proteolytic degradation [62,63].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [62] Jones AM Elliott T A purified mutant HemA protein from Salmonella enterica serovar Typhimurium lacks bound heme and is defective for heme-mediated regulation in vivo FEMS Microbiol Lett 307 2010 41 47 20412302 source
- Not checked yetcites [63] Wang L Wilson S Elliott T A mutant HemA protein with positive charge close to the N terminus is stabilized against heme-regulated proteolysis in Salmonella typhimurium J Bacteriol 181 1999 6033 6041 10498716 PMC103631 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Two promoters exist upstream of hemA in the Gram-negative pathogen Pseudomonas aeruginosa, and these promoters contain binding sites for the regulators Anr (oxygen sensing), Dnr (redox regulator), IHF (integration host factor), and NarL (nitrate regulator) [66,67].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [66] Krieger R Rompf A Schobert M Jahn D The Pseudomonas aeruginosa hemA promoterisregulatedby Anr, Dnr, NarL and Integration Host Factor Mol Gen Genomics 267 2002 409 417 12073043 source
- Not checked yetcites [67] Hungerer C Troup B Romling U Jahn D Regulation of the hemA gene during 5-aminolevulinic acid formation in Pseudomonas aeruginosa J Bacteriol 177 1995 1435 1443 7883699 PMC176757 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“This was explained by the observation that excess heme results in the proteolytic degradation of HemA in Salmonella, suggesting that HemA might bind excess heme [60].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [60] Wang LY Brown L Elliott M Elliott T Regulation of heme biosynthesis in Salmonella typhimurium: activity of glutamyl-tRNA reductase (HemA) is greatly elevated during heme limitation by a mechanism which increases abundance of the protein J Bacteriol 179 1997 2907 2914 9139907 PMC179053 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In B. subtilis, hemEHY is induced anaerobically and hemAXCBL is induced by peroxide through de-repression of PerR [38,68].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [38] Hansson M Rutberg L Schroder I Hederstedt L The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes of the biosynthetic pathway from glutamate to uroporphyrinogen III J Bacteriol 173 1991 2590 2599 1672867 PMC207825 source
- Not checked yetcites [68] Ye RW Tao W Bedzyk L Young T Chen M Li L Global gene expression profiles of Bacillus subtilis grown under anaerobic conditions J Bacteriol 182 2000 4458 4465 10913079 PMC94617 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, hemA expression is induced in the presence of oxygen or when oxygen is lacking but an alternative electron acceptor such as nitrate is present for utilization of heme-dependent respiration.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Homologs of B. subtilis HemX exist in multiple Gram-positive pathogens; however, the function of HemX and HemA regulation has yet to be detailed.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Regulation of heme synthesis
What the sources say
- Not checked yetcites [38] Hansson M Rutberg L Schroder I Hederstedt L The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes of the biosynthetic pathway from glutamate to uroporphyrinogen III J Bacteriol 173 1991 2590 2599 1672867 PMC207825 source
- Not checked yetcites [65] Schroder I Johansson P Rutberg L Hederstedt L The hemX gene of the Bacillus subtilis hemAXCDBL operon encodes a membrane protein, negatively affecting the steady-state cellular concentration of HemA (glutamyl-tRNA reductase) Microbiology 140 1994 731 740 8012594 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For S. aureus, in which heme synthesis and acquisition are vital during infection, the regulation of heme synthesis is unknown.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Current challenges and opportunities
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This results in accessible free heme, heme bound by hemopexin (Hx), free Hb (Hb), and Hb bound by Hp to form the Hp–Hbcomplex.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For S. aureus, whose reliance on heme acquisition during infection has been well established, it is now clear that heme biosynthesis is vital to cause disease in murine models of infection [84–86].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [84] Skaar EP Humayun M Bae T DeBord KL Schneewind O Iron-source preference of Staphylococcus aureus infections Science 305 2004 1626 1628 15361626 source
- Not checked yetcites [85] Pishchany G Sheldon JR Dickson CF Alam MT Read TD Gell DA IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus J Infect Dis 209 2014 1764 1772 24338348 PMC4038968 source
- Not checked yetcites [86] Pishchany G McCoy AL Torres VJ Krause JC Crowe JE Jr Fabry ME Specificity for human hemoglobin enhances Staphylococcus aureus infection Cell Host Microbe 8 2010 544 550 21147468 PMC3032424 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For other pathogens, the contribution of heme synthesis to disease is still unclear, but whole-genome in vivo fitness experiments like transposon-sequencing suggest many bacterial pathogens rely on heme biosynthesis to cause disease”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Current challenges and opportunities
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Heme acquired from the host is used fully intact or degraded to liberate heme-iron and both processes are important during bacterial pathogenesis.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies
What the sources say
- Not checked yetcites [115] Skaar EP Gaspar AH Schneewind O IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus J Biol Chem 279 2004 436 443 14570922 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, like S. aureus, host heme utilization is insufficient and synthesis is required for full virulence.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the contribution of heme synthesis to the pathogenesis of bacterial pathogens is largely understudied.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Despite their reduced virulence, SCVs are generally more resistant to antibiotics and oxidative stress, more equipped to evade the immune system by living intracellularly, and are likely the etiological agent of persistent staphylococcal infections [89–92]”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [89] von Eiff C Heilmann C Proctor RA Woltz C Peters G Gotz F A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly J Bacteriol 179 1997 4706 4712 9244256 PMC179315 source
- Not checked yetcites [90] Balwit JM van Langevelde P Vann JM Proctor RA Gentamicin-resistant menadione and hemin auxotrophic Staphylococcus aureus persist within cultured endothelial cells J Infect Dis 170 1994 1033 1037 7930701 source
- Not checked yetcites [91] Painter KL Strange E Parkhill J Bamford KB Armstrong-James D Edwards AM Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response Infect Immun 83 2015 1830 1844 25690100 PMC4399076 source
- Not checked yetcites [92] Sadowska B Bonar A von Eiff C Proctor RA Chmiela M Rudnicka W Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants FEMS Immunol Med Microbiol 32 2002 191 197 11934563 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The Isd system enables utilization of free heme, or heme bound to Hb and Hp–Hb complexes.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Inactivation of hemA, which renders S. aureus heme deficient, causes the small-colony variant (SCV) phenotype [87].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
What the sources say
- Not checked yetcites [87] Hammer ND Reniere ML Cassat JE Zhang Y Hirsch AO Hood MI Two heme-dependent terminal oxidases power Staphylococcus aureus organ-specific colonization of the vertebrate host mBio 4 2013 PMC3735196 23900169 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data demonstrate that for S. aureus, heme acquisition is insufficient to support organ colonization and therefore heme biosynthesis is critical to pathogenesis.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Contribution of heme synthesis to pathogenesis
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Small molecules have been described that modulate heme synthesis in vivo, while in vitro inhibitors of S. aureus HemY have recently been reported, suggesting that Gram-positive heme synthesis is an attractive drug target [52,99,100].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Bacterial Heme Synthesis > Current challenges and opportunities
What the sources say
- Not checked yetcites [52] Lobo SA Scott A Videira MA Winpenny D Gardner M Palmer MJ Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway Mol Microbiol 97 2015 472 487 25908396 source
- Not checked yetcites [99] Mike LA Dutter BF Stauff DL Moore JL Vitko NP Aranmolate O Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus Proc Natl Acad Sci USA 110 2013 9206 8211 PMC3657828 23630262 source
- Not checked yetcites [100] Dutter BF Mike LA Reid PR Chong KM Ramos-Hunter SJ Skaar EP Decoupling activation of heme biosynthesis from anaerobic toxicity in a molecule active in Staphylococcus aureus ACS Chem Biol 2016 PMID: 26890615, Epub ahead of print http://dx.doi.org/10.1021/acschembio.5b00934 PMC5117894 26890615 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“S. aureus encodes an iron-regulated Sortase B (SrtB) for which IsdC is the only substrate, and SrtB attaches IsdC to peptidoglycan in such a way that IsdC is not surface exposed but rather buried in the cell wall, which is 15–30 nm thick [112,113].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [112] Mazmanian SK Ton-That H Su K Schneewind O An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis Proc Natl Acad Sci USA 99 2002 2293 2298 11830639 PMC122358 source
- Not checked yetcites [113] Beveridge J Ultrastructure of Gram-positive cell walls Fishetti VA Novick RP Feretti JJ Portnoy DA Rood JI Gram-Positive Pathogens second ASM Press Washington, DC 2000 3 10
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IsdB contains two NEAT domains, NEAT1 (N1) binds Hb and Hb–Hp, but not Hp and N2 binds heme; as such IsdB is believed to be the primary Hb-binding protein [85,107,108].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [85] Pishchany G Sheldon JR Dickson CF Alam MT Read TD Gell DA IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus J Infect Dis 209 2014 1764 1772 24338348 PMC4038968 source
- Not checked yetcites [107] Fonner BA Tripet BP Eilers BJ Stanisich J Sullivan-Springhetti RK Moore R Solution structure and molecular determinants of hemoglobin binding of the first NEAT domain of IsdB in Staphylococcus aureus Biochemistry 53 2014 3922 3933 24871270 PMC4072347 source
- Not checked yetcites [108] Torres VJ Pishchany G Humayun M Schneewind O Skaar EP Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization J Bacteriol 188 2006 8421 8429 17041042 PMC1698231 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, IsdHN1 and N2 bind Hb and Hp, and IsdH-N3 extracts the heme.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [111] Muryoi N Tiedemann MT Pluym M Cheung J Heinrichs DE Stillman MJ Demonstration of the iron-regulated surface determinant (Isd) heme transfer pathway in Staphylococcus aureus J Biol Chem 283 2008 28125 28136 18676371 PMC2661384 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IsdG and IsdI are structurally similar and are the first described members of the Isd heme oxygenase family, which catabolizes heme to staphylobilin instead of biliverdin [117–119].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [117] Reniere ML Ukpabi GN Harry SR Stec DF Krull R Wright DW The IsdG-family of haem oxygenases degrades haem to a novel chromophore Mol Microbiol 75 2010 1529 1538 20180905 PMC3800195 source
- Not checked yetcites [118] Lee WC Reniere ML Skaar EP Murphy ME Ruffling of metalloporphyrins bound to IsdG and IsdI, two hemed-egrading enzymes in Staphylococcus aureus J Biol Chem 283 2008 30957 30963 18713745 PMC2576546 source
- Not checked yetcites [119] Wu R Skaar EP Zhang R Joachimiak G Gornicki P Schneewind O Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural similarity to monooxygenases J Biol Chem 280 2005 2840 2846 15520015 PMC2792019 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Upon import, heme is incorporated into staphylococcal proteins or degraded.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [115] Skaar EP Gaspar AH Schneewind O IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus J Biol Chem 279 2004 436 443 14570922 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IsdG and IsdI are required for growth using heme as a sole iron source and are expressed during infection [115,120].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [115] Skaar EP Gaspar AH Schneewind O IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus J Biol Chem 279 2004 436 443 14570922 source
- Not checked yetcites [120] Reniere ML Skaar EP Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem Mol Microbiol 69 2008 1304 1315 18643935 PMC2597461 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“IsdA, which is partially surface exposed, contains a single heme-binding NEAT domain [102].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [102] Mazmanian SK Skaar EP Gaspar AH Humayun M Gornicki P Jelenska J Passage of heme-iron across the envelope of Staphylococcus aureus Science 299 2003 906 909 12574635 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The current model (Fig. 2), supported by strong structural evidence, suggests that IsdB-N1 binds Hb, and IsdB-N2 extracts heme [111].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [111] Muryoi N Tiedemann MT Pluym M Cheung J Heinrichs DE Stillman MJ Demonstration of the iron-regulated surface determinant (Isd) heme transfer pathway in Staphylococcus aureus J Biol Chem 283 2008 28125 28136 18676371 PMC2661384 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The NEAT domains are 120–125 aa domains that constitute a conserved eight-stranded β-sandwich fold [104,105].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [104] Grigg JC Vermeiren CL Heinrichs DE Murphy ME Haem recognition by a Staphylococcus aureus NEAT domain Mol Microbiol 63 2007 139 149 17229211 source
- Not checked yetcites [105] Sharp KH Schneider S Cockayne A Paoli M Crystal structure of the heme-IsdC complex, the central conduit of the Isd iron/heme uptake system in Staphylococcus aureus J Biol Chem 282 2007 10625 10631 17287214 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Exogenous heme accumulates in the membrane and is also capable of complementing the growth of heme-deficient mutants [84].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [84] Skaar EP Humayun M Bae T DeBord KL Schneewind O Iron-source preference of Staphylococcus aureus infections Science 305 2004 1626 1628 15361626 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Further regulation of the heme oxygenases exists; IsdG abundance increases in the presence of heme and IsdG half-life is increased when heme-bound [120].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [120] Reniere ML Skaar EP Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem Mol Microbiol 69 2008 1304 1315 18643935 PMC2597461 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The heme is then transferred either directly to IsdC or shuttled via IsdA to IsdC.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [111] Muryoi N Tiedemann MT Pluym M Cheung J Heinrichs DE Stillman MJ Demonstration of the iron-regulated surface determinant (Isd) heme transfer pathway in Staphylococcus aureus J Biol Chem 283 2008 28125 28136 18676371 PMC2661384 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IsdH contains three NEAT domains, N1 and N2 bind both Hb and Hp, andN3bindsheme [109,110].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [109] Dryla A Gelbmann D Von Gabain A Nagy E Identification of a novel iron regulated staphylococcal surface protein with haptoglobin-haemoglobin binding activity Mol Microbiol 49 2003 37 53 12823809 source
- Not checked yetcites [110] Pilpa RM Robson SA Villareal VA Wong ML Phillips M Clubb RT Functionally distinct NEAT (NEAr Transporter) domains within the Staphylococcus aureus IsdH/HarA protein extract heme from methemoglobin J Biol Chem 284 2009 1166 1176 18984582 PMC2613621 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A guinea pig infection model demonstrated that ΔisdCX1X2 was as virulent as wild type, yet these proteins are expressed during infection [134].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [134] Gat O Zaide G Inbar I Grosfeld H Chitlaru T Levy H Characterization of Bacillus anthracis iron-regulated surface determinant (Isd) proteins containing NEAT domains Mol Microbiol 70 2008 983 999 18826411 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“IsdX1 contains one NEAT domain, while IsdX2 contains five NEAT domains; both are secreted past the cell wall as they lack sortase signals or membrane spanning domains [125].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [125] Maresso AW Garufi G Schneewind O Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin PLoS Pathog 4 2008 e1000132 18725935 PMC2515342 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“B. anthracis also encodes other NEAT contain proteins; Hal contains a single NEAT domain and leucine-rich repeats, which extract heme from Hb [130].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [130] Balderas MA Nobles CL Honsa ES Alicki ER Maresso AW Hal Is a Bacillus anthracis heme acquisition protein J Bacteriol 194 2012 5513 5521 22865843 PMC3458686 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These are the first described Gram-positive hemophores and bind heme, Hb, and methemoglobin [125– 129].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [125] Maresso AW Garufi G Schneewind O Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin PLoS Pathog 4 2008 e1000132 18725935 PMC2515342 source
- Not checked yetcites [126] Fabian M Solomaha E Olson JS Maresso AW Heme transfer to the bacterial cell envelope occurs via a secreted hemophore in the Gram-positive pathogen Bacillus anthracis J Biol Chem 284 2009 32138 32146 19759022 PMC2797284 source
- Not checked yetcites [127] Honsa ES Fabian M Cardenas AM Olson JS Maresso AW The five near-iron transporter (NEAT) domain anthrax hemophore, IsdX2, scavenges heme from hemoglobin and transfers heme to the surface protein IsdC J Biol Chem 286 2011 33652 33660 21808055 PMC3190864 source
- Not checked yetcites [128] Maresso AW Chapa TJ Schneewind O Surface protein IsdC and Sortase B are required for heme-iron scavenging of Bacillus anthracis J Bacteriol 188 2006 8145 8152 17012401 PMC1698196 source
- Not checked yetcites [129] Honsa ES Owens CP Goulding CW Maresso AW The near-iron transporter (NEAT) domains of the anthrax hemophore IsdX2 require a critical glutamine to extract heme from methemoglobin J Biol Chem 288 2013 8479 8490 23364793 PMC3605663 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The current proposed model (Fig. 2) is that IsdX1 is secreted, binds heme, and transfers heme to wall-anchored IsdC.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [125] Maresso AW Garufi G Schneewind O Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin PLoS Pathog 4 2008 e1000132 18725935 PMC2515342 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“B. anthracis encodes a heme uptake system that shares the core of the S. aureus Isd, but with additional unique proteins.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [125] Maresso AW Garufi G Schneewind O Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin PLoS Pathog 4 2008 e1000132 18725935 PMC2515342 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The diversity of heme and Hb-binding proteins relative to S. aureus may be the result of the greater variety of environmental niches that germinant and sporulent B. anthracis inhabits.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is likely that the IsdX1/X2 hemophores, BslK, and Hal are partially redundant, and a mutant lacking all four proteins would be highly defective in causing anthrax.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A second, recently described NEAT protein is BslK, which is non-covalently attached to the cell wall and transfers heme to IsdC [132].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [132] Tarlovsky Y Fabian M Solomaha E Honsa E Olson JS Maresso AW A Bacillus anthracis S-layer homology protein that binds heme and mediates heme delivery to IsdC J Bacteriol 192 2010 3503 3511 20435727 PMC2897652 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Heme is the preferred iron-source during systemic infection, in part because a heme-responsive transcriptional regulator activates iron siderophore synthesis only when heme-iron is unavailable [84,122].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [84] Skaar EP Humayun M Bae T DeBord KL Schneewind O Iron-source preference of Staphylococcus aureus infections Science 305 2004 1626 1628 15361626 source
- Not checked yetcites [122] Laakso HA Marolda CL Pinter TB Stillman MJ Heinrichs DE A heme-responsive regulator controls synthesis of Staphyloferrin B in Staphylococcus aureus J Biol Chem 291 2016 29 40 26534960 PMC4697164 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“IsdX2 can bind free heme, accept heme from IsdX1, and transfer heme to IsdC.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > Isd-dependent heme uptake by B. anthracis
What the sources say
- Not checked yetcites [125] Maresso AW Garufi G Schneewind O Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin PLoS Pathog 4 2008 e1000132 18725935 PMC2515342 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutants lacking components of the Isd system are highly defective inpathogenesis, highlighting the importance of heme acquisition to staphylo-coccal disease [84–86,108,120,123,124].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > The S. aureus Isd paradigm
What the sources say
- Not checked yetcites [84] Skaar EP Humayun M Bae T DeBord KL Schneewind O Iron-source preference of Staphylococcus aureus infections Science 305 2004 1626 1628 15361626 source
- Not checked yetcites [85] Pishchany G Sheldon JR Dickson CF Alam MT Read TD Gell DA IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus J Infect Dis 209 2014 1764 1772 24338348 PMC4038968 source
- Not checked yetcites [86] Pishchany G McCoy AL Torres VJ Krause JC Crowe JE Jr Fabry ME Specificity for human hemoglobin enhances Staphylococcus aureus infection Cell Host Microbe 8 2010 544 550 21147468 PMC3032424 source
- Not checked yetcites [108] Torres VJ Pishchany G Humayun M Schneewind O Skaar EP Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization J Bacteriol 188 2006 8421 8429 17041042 PMC1698231 source
- Not checked yetcites [120] Reniere ML Skaar EP Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem Mol Microbiol 69 2008 1304 1315 18643935 PMC2597461 source
- Not checked yetcites [123] Visai L Yanagisawa N Josefsson E Tarkowski A Pezzali I Rooijakkers SH Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH Microbiology 155 2009 667 679 19246738 source
- Not checked yetcites [124] Cheng AG Kim HK Burts ML Krausz T Schneewind O Missiakas DM Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues FASEB J 23 2009 3393 3404 19525403 PMC2747682 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition to heme, HtaA can acquire heme from Hb and transfer heme to HtaB, suggesting a heme shuttle from HtaA toHtaB toHmuT; HmuT isa surface-anchored lipoprotein, which then transfers heme to the cognate ABC transporter HmuUV [148].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [148] Allen CE Schmitt MP Novel hemin binding domains in the Corynebacterium diphtheriae HtaA protein interact with hemoglobin and are critical for heme iron utilization by HtaA J Bacteriol 193 2011 5374 5385 21803991 PMC3187408 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It appears that these heme-binding proteins serve redundant functions, and as such, a mutant lacking both HtaB and ChtB is deficient at utilizing Hb as an iron source [152].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [152] Allen CE Burgos JM Schmitt MP Analysis of novel iron-regulated, surface-anchored hemin-binding proteins in Corynebacterium diphtheriae J Bacteriol 195 2013 2852 2863 23585541 PMC3697262 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The current model (Fig. 2) for Hp–Hb heme acquisition involves binding of Hp–Hb by a combination of HtaA and ChtA or ChtC, heme extraction either actively or passively, and transfer to HtaB, HmuT, and HmuUV [153].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [153] Allen CE Schmitt MP Utilization of host iron sources by Corynebacterium diphtheriae: multiple hemoglobin-binding proteins are essential for the use of iron from the hemoglobin– haptoglobin complex J Bacteriol 197 2015 553 562 25404705 PMC4285985 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DtxR is the Diphtheria Toxin regulator which activates the expression of Diphtheria Toxin as well as HmuTUV and HtaABC [150,151].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [150] Kunkle CA Schmitt MP Analysis of a DtxR-regulated iron transport and siderophore biosynthesis gene cluster in Corynebacterium diphtheriae J Bacteriol 187 2005 422 433 15629913 PMC543566 source
- Not checked yetcites [151] Kunkle CA Schmitt MP Analysis of the Corynebacterium diphtheriae DtxR regulon: identification of a putative siderophore synthesis and transport system that is similar to the Yersinia high-pathogenicity island-encoded yersiniabactin synthesis and uptake system J Bacteriol 185 2003 6826 6840 14617647 PMC262719 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This results in surface exposure of HtaA and HtaB, which both bind heme.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Adjacent to this locus are the genes htaB and htaC.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [147] Allen CE Schmitt MP HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae J Bacteriol 191 2009 2638 2648 19201805 PMC2668399 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, Gram-negative heme uptake systems consist of outer-membrane receptors that either bind heme and hemoproteins directly, or bind heme-bound secreted hemophores.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Like HtaAB, ChtAB and CirAChtC are surface exposed and ChtAB and ChtC bind heme and Hb.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [152] Allen CE Burgos JM Schmitt MP Analysis of novel iron-regulated, surface-anchored hemin-binding proteins in Corynebacterium diphtheriae J Bacteriol 195 2013 2852 2863 23585541 PMC3697262 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The versatile opportunistic pathogen P. aeruginosa encodes direct heme uptake and hemophore systems at the outer membrane, H. influenzae uses a hemophore uptake system, and Neisseria meningitidis uses a unique bipartite receptor for heme acquisition from host hemoproteins .”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies
What the sources say
- Not checked yetcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 source
- Not checked yetcites [155] Letoffe S Nato F Goldberg ME Wandersman C Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR Mol Microbiol 33 1999 546 555 10417645 source
- Not checked yetcites [156] Letoffe S Deniau C Wolff N Dassa E Delepelaire P Lecroisey A Haemophore-mediated bacterial haem transport: evidence for a common or overlapping site for haem-free and haem-loaded haemophore on its specific outer membrane receptor Mol Microbiol 41 2001 439 450 11489129 source
- Not checked yetcites [157] Smith AD Wilks A Differential contributions of the outer membrane receptors PhuR and HasR to heme acquisition in Pseudomonas aeruginosa J Biol Chem 290 2015 7756 7766 25616666 PMC4367277 source
- Not checked yetcites [158] Oglesby-Sherrouse AG Vasil ML Characterization of a heme-regulated non-coding RNA encoded by the prrF locus of Pseudomonas aeruginosa PLoS One 5 2010 e9930 20386693 PMC2851614 source
- Not checked yetcites [159] Reinhart AA Powell DA Nguyen AT O'Neill M Djapgne L Wilks A The prrF-encoded small regulatory RNAs are required for iron homeostasis and virulence of Pseudomonas aeruginosa Infect Immun 83 2015 863 875 25510881 PMC4333466 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The associated heme oxygenase, HmuO, was discovered and described first, and then HmuTUV was discovered for the ability of a plasmid encoding hmuTUV to complement a Corynebacterium ulcerans strain that cannot grow on Hb as a sole iron source [144,145].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [144] Schmitt MP Utilization of host iron sources by Coryne-bacterium diphtheriae: identification of a gene whose product is homologous to eukaryotic heme oxygenases and is required for acquisition of iron from heme and hemoglobin J Bacteriol 179 1997 838 845 9006041 PMC178768 source
- Not checked yetcites [145] Drazek ES Hammack CA Schmitt MP Corynebacterium diphtheriae genes required for acquisition of iron from haemin and haemoglobin are homologous to ABC haemin transporters Mol Microbiol 36 2000 68 84 10760164 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“HtaA isolated from cell culture is unable to complement the growth of an htaA mutant, suggesting that surface bound HtaA may serve as a heme receptor and secreted HtaA may serve as a hemophore [147,148].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [147] Allen CE Schmitt MP HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae J Bacteriol 191 2009 2638 2648 19201805 PMC2668399 source
- Not checked yetcites [148] Allen CE Schmitt MP Novel hemin binding domains in the Corynebacterium diphtheriae HtaA protein interact with hemoglobin and are critical for heme iron utilization by HtaA J Bacteriol 193 2011 5374 5385 21803991 PMC3187408 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“While the Isd NEAT domains rely on tyrosine alone as the axial ligand for heme binding, HmuT relies on an N-terminal histidine and a C-terminal tyrosine to coordinate heme [149].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [149] Draganova EB Akbas N Adrian SA Lukat-Rodgers GS Collins DP Dawson JH Heme binding by Corynebacterium diphtheriae HmuT: function and heme environment Biochemistry 54 2015 6598 6609 26478504 PMC4943319 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recently, it has been shown that ChtA and ChtC are both capable of binding Hp–Hb for heme extraction, and acquisition of heme from Hp–Hb requires HtaA [153].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Positive Heme Acquisition Strategies > C. diphtheriae heme uptake
What the sources say
- Not checked yetcites [153] Allen CE Schmitt MP Utilization of host iron sources by Corynebacterium diphtheriae: multiple hemoglobin-binding proteins are essential for the use of iron from the hemoglobin– haptoglobin complex J Bacteriol 197 2015 553 562 25404705 PMC4285985 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Heme then transits the periplasm and is brought into the cell via ABC transporters at the inner membrane.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies
What the sources say
- Not checked yetcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Data from the orthologous HasA hemophore of Serratia marcescens suggest that HasA binds Hb and extracts heme, then HasA transfers heme to HasR [155,156].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [155] Letoffe S Nato F Goldberg ME Wandersman C Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR Mol Microbiol 33 1999 546 555 10417645 source
- Not checked yetcites [156] Letoffe S Deniau C Wolff N Dassa E Delepelaire P Lecroisey A Haemophore-mediated bacterial haem transport: evidence for a common or overlapping site for haem-free and haem-loaded haemophore on its specific outer membrane receptor Mol Microbiol 41 2001 439 450 11489129 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In contrast to many other organisms, Pseudomonas encodes a soluble cytoplasmic heme-binding protein that is not a heme oxygenase.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [160] Lansky IB Lukat-Rodgers GS Block D Rodgers KR Ratliff M Wilks A The cytoplasmic heme-binding protein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is an intracellular heme-trafficking protein to the delta-regioselective heme oxygenase J Biol Chem 281 2006 13652 13662 16533806 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“When heme is available, HasS instead binds HasR, and HasI is free to recruit RNA polymerase to activate the transcription of hasAR, hasSI, phuSTUV, and phuR [157].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [157] Smith AD Wilks A Differential contributions of the outer membrane receptors PhuR and HasR to heme acquisition in Pseudomonas aeruginosa J Biol Chem 290 2015 7756 7766 25616666 PMC4367277 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The present model (Fig. 3) for these two heme uptake systems suggests that Phu is the principle heme acquisition system but full heme utilization requires HasA/HasR.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [157] Smith AD Wilks A Differential contributions of the outer membrane receptors PhuR and HasR to heme acquisition in Pseudomonas aeruginosa J Biol Chem 290 2015 7756 7766 25616666 PMC4367277 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The Phu (Pseudomonas heme uptake) consists of a TonB-dependent PhuR which binds heme and transports it to the periplasm.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“HasA is a secreted hemophore that binds heme and transfers it to a second TonB-dependent transporter, HasR.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [155] Letoffe S Nato F Goldberg ME Wandersman C Interactions of HasA, a bacterial haemophore, with haemoglobin and with its outer membrane receptor HasR Mol Microbiol 33 1999 546 555 10417645 source
- Not checked yetcites [156] Letoffe S Deniau C Wolff N Dassa E Delepelaire P Lecroisey A Haemophore-mediated bacterial haem transport: evidence for a common or overlapping site for haem-free and haem-loaded haemophore on its specific outer membrane receptor Mol Microbiol 41 2001 439 450 11489129 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“PhuR activity is representative of Gram-negative TonB-dependent outer-membrane receptors.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Further in vitro characterization and structural analysis has led to a model whereby heme coordination occurs primarily at the His212 ligand and induces a conformational change required for interaction with HemO [162,163].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [162] Tripathi S O'Neill MJ Wilks A Poulos TL Crystal structure of the Pseudomonas aeruginosa cytoplasmic heme binding protein, Apo-PhuS J Inorg Biochem 128 2013 131 136 23973453 PMC3843485 source
- Not checked yetcites [163] O'Neill MJ Bhakta MN Fleming KG Wilks A Induced fit on heme binding to the Pseudomonas aeruginosa cytoplasmic protein (PhuS) drives interaction with heme oxygenase (HemO) Proc Natl Acad Sci USA 109 2012 5639 5644 22451925 PMC3326490 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These β-barrel proteins bind substrates (often iron containing molecules) with high affinity, and rely on proton motive force and TonB for transport across the outer membrane [154].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [154] Noinaj N Guillier M Barnard TJ Buchanan SK TonB-dependent transporters: regulation, structure, and function Annu Rev Microbiol 64 2010 43 60 20420522 PMC3108441 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“HasA/HasR may be more relevant as a heme sensing system; under low heme conditions, the inner-membrane HasS binds the sigma factor inhibitor HasI.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > P. aeruginosa
What the sources say
- Not checked yetcites [157] Smith AD Wilks A Differential contributions of the outer membrane receptors PhuR and HasR to heme acquisition in Pseudomonas aeruginosa J Biol Chem 290 2015 7756 7766 25616666 PMC4367277 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“demonstrates high-affinity binding specifically to Hx with little distinction between apo- and holo-Hx [172].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [172] Fournier C Smith A Delepelaire P Haem release from haemopexin by HxuA allows Haemophilus influenzae to escape host nutritional immunity Mol Microbiol 80 2011 133 148 21276097 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“capable of binding Hb, apo-Hp, and Hp–Hb [190,191].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [190] Lewis LA Gray E Wang YP Roe BA Dyer DW Molecular characterization of hpuAB, the haemoglobin–hapto-globin-utilization operon of Neisseria meningitidis Mol Microbiol 23 1997 737 749 9157245 source
- Not checked yetcites [191] Lewis LA Dyer DW Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin J Bacteriol 177 1995 1299 1306 7868605 PMC176737 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“HxuC is a TonB-dependent transporter that binds heme after release from the Hx–heme–HxuA complex and imports it into the periplasm [173].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
What the sources say
- Not checked yetcites [173] Cope LD Love RP Guinn SE Gilep A Usanov S Estabrook RW Involvement of HxuC outer membrane protein in utilization of hemoglobin by Haemophilus influenzae Infect Immun 69 2001 2353 2363 11254593 PMC98165 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Heme is extracted from these hemoproteins and is imported intact”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [194] Lewis LA Sung MH Gipson M Hartman K Dyer DW Transport of intact porphyrin by HpuAB, the hemoglobin– haptoglobin utilization system of Neisseria meningitidis J Bacteriol 180 1998 6043 6047 9811666 PMC107682 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Like HpuAB, it is subject to phase variation [202].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [202] Richardson AR Stojiljkovic I HmbR, a hemoglobin-binding outer membrane protein of Neisseria meningitidis, undergoes phase variation J Bacteriol 181 1999 2067 2074 10094683 PMC93618 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“HmbR (Hb receptor) is an additional N. meningitidis heme uptake protein that binds host Hb with species specificity, exhibiting a greater utilization of human Hb”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [200] Stojiljkovic I Hwa V de Saint Martin L O'Gaora P Nassif X Heffron F The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence Mol Microbiol 15 1995 531 541 7783623 source
- Not checked yetcites [201] Stojiljkovic I Larson J Hwa V Anic S So M HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation J Bacteriology 178 1996 4670 4678 PMC178238 8755899 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“HpuA is required for growth with Hb as a sole iron source and heme import [198].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [198] Rohde KH Gillaspy AF Hatfield MD Lewis LA Dyer DW Interactions of haemoglobin with the Neisseria meningitidis receptor HpuAB: the role of TonB and an intact proton motive force Mol Microbiol 43 2002 335 354 11985713 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“they suggest that HpuA and HpuA homologs interact with Hb, and this interaction is required for HpuAB-mediate heme uptake.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [199] Wong CT Xu Y Gupta A Garnett JA Matthews SJ Hare SA Structural analysis of haemoglobin binding by HpuA from the Neisseriaceae family Nat Commun 6 2015 10172 26671256 PMC4703857 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Paradoxically, excess heme is toxic and thus during infection, invading pathogens must contend with heme toxicity as a component of pathogenesis.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance
What the sources say
- Not checked yetcites [25] Everse J Hsia N The toxicities of native and modified hemoglobins Free Radic Biol Med 22 1997 1075 1099 9034247 source
- Not checked yetcites [219] Chou AC Fitch CD Mechanism of hemolysis induced by ferriprotoporphyrin IX J Clin Invest 68 1981 672 677 7276166 PMC370848 source
- Not checked yetcites [220] Schmitt TH Frezzatti WA Jr Schreier S Hemin-induced lipid membrane disorder and increased permeability: a molecular model for the mechanism of cell lysis Arch Biochem Biophys 307 1993 96 103 8239671 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“is unable to bind the Hp-Hb complex and therefore likely binds free Hb only [200,201].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > N. meningitidis
What the sources say
- Not checked yetcites [200] Stojiljkovic I Hwa V de Saint Martin L O'Gaora P Nassif X Heffron F The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence Mol Microbiol 15 1995 531 541 7783623 source
- Not checked yetcites [201] Stojiljkovic I Larson J Hwa V Anic S So M HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation J Bacteriology 178 1996 4670 4678 PMC178238 8755899 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In heme stress, hrtAB and pefAB/RCD are expressed at high levels, and the Pef systems are required for resistance to heme toxicity [223].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [223] Fernandez A Lechardeur D Derre-Bobillot A Couve E Gaudu P Gruss A Two coregulated efflux transporters modulate intracellular heme and protoporphyrin IX availability in Streptococcus agalactiae PLoS Pathog 6 2010 e1000860 20421944 PMC2858704 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“this work also localized heme toxicity primarily to the membrane.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [228] Wakeman CA Hammer ND Stauff DL Attia AS Anzaldi LL Dikalov SI Menaquinone biosynthesis potentiates haem toxicity in Staphylococcus aureus Mol Microbiol 86 2012 1376 1392 23043465 PMC3524387 source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The accumulation of heme results in excess iron by one of two mechanisms, both of which are likely at play under aerobic conditions.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Superoxide production is a separate source of oxidative damage from ferrous iron-mediated ROS and is a major component of heme damage in S. aureus [228].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [228] Wakeman CA Hammer ND Stauff DL Attia AS Anzaldi LL Dikalov SI Menaquinone biosynthesis potentiates haem toxicity in Staphylococcus aureus Mol Microbiol 86 2012 1376 1392 23043465 PMC3524387 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Streptococcus agalactiae encodes an orthologue of HrtAB, as well as a dual efflux system PefAB and PefRCD [223].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [223] Fernandez A Lechardeur D Derre-Bobillot A Couve E Gaudu P Gruss A Two coregulated efflux transporters modulate intracellular heme and protoporphyrin IX availability in Streptococcus agalactiae PLoS Pathog 6 2010 e1000860 20421944 PMC2858704 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In B. anthracis, an HssRS orthologue controls the expression of HrtAB and cross-talks with a second TCS that responds to cellular envelope stresses”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
What the sources say
- Not checked yetcites [238] Mike LA Choby JE Brinkman PR Olive LQ Dutter BF Ivan SJ Two-component system cross-regulation integrates Bacillus anthracis response to heme and cell envelope stress PLoS Pathog 10 2014 e1004044 24675902 PMC3968170 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“non-iron protoporphyrins are toxic to bacteria and activate the cellular response to heme toxicity [229–231].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [229] Wakeman CA Stauff DL Zhang Y Skaar EP Differential activation of Staphylococcus aureus heme detoxification machinery by heme analogues J Bacteriol 196 2014 1335 1342 24443529 PMC3993332 source
- Not checked yetcites [230] Stojiljkovic I Kumar V Srinivasan N Non-iron metalloporphyrins: potent antibacterial compounds that exploit haem/Hb uptake systems of pathogenic bacteria Mol Microbiol 31 1999 429 442 10027961 source
- Not checked yetcites [231] Nitzan Y Wexler HM Finegold SM Inactivation of anaerobic bacteria by various photosensitized porphyrins or by hemin Curr Microbiol 29 1994 125 131 7765091 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additional efflux systems exist, suggesting that this strategy is well conserved.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Strategies to overcome heme toxicity
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“suggesting that damage by heme is similar to other hydrophobic molecules and may disrupt the Gram-negative outer membrane [224,233].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [224] Rasmussen AW Alexander HL Perkins-Balding D Shafer WM Stojiljkovic I Resistance of Neisseria meningitidis to the toxic effects of heme iron and other hydrophobic agents requires expression of ght J Bacteriol 187 2005 5214 5223 16030215 PMC1196014 source
- Not checked yetcites [233] Putker F Grutsch A Tommassen J Bos MP Ght protein of Neisseria meningitidis is involved in the regulation of lipopoly-saccharide biosynthesis J Bacteriol 196 2014 780 789 24296673 PMC3911185 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In conditions of excess heme toxicity, membrane proteins are highly oxidized and superoxide is formed by redox cycling of heme-iron through membrane menaquinone [228].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [228] Wakeman CA Hammer ND Stauff DL Attia AS Anzaldi LL Dikalov SI Menaquinone biosynthesis potentiates haem toxicity in Staphylococcus aureus Mol Microbiol 86 2012 1376 1392 23043465 PMC3524387 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The lipophilic nature of heme suggests that it partitions to the membrane of bacteria, and this has been demonstrated in S. aureus, likely resulting in damage to membrane proteins and lipids [84].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Multi-faceted mechanism of heme toxicity
What the sources say
- Not checked yetcites [84] Skaar EP Humayun M Bae T DeBord KL Schneewind O Iron-source preference of Staphylococcus aureus infections Science 305 2004 1626 1628 15361626 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the Hb-binding IsdB of S. aureus exhibits species specificity and more efficiently utilizes human Hb relative to mouse Hb [86].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > Current challenges and opportunities
What the sources say
- Not checked yetcites [86] Pishchany G McCoy AL Torres VJ Krause JC Crowe JE Jr Fabry ME Specificity for human hemoglobin enhances Staphylococcus aureus infection Cell Host Microbe 8 2010 544 550 21147468 PMC3032424 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on limited evidence, exogenous heme is preferred when available”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Concluding Remarks
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“additional properties like oxygenase (PhuS and ChuS) and DNA binding (ShuS) have been observed.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Heme Toxicity and Tolerance > Current challenges and opportunities
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“the Mycobacterium tuberculosis heme uptake system, which comprises three unique proteins and is sufficient to rescue the growth of a heme auxotroph”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > Current challenges and opportunities
What the sources say
- Not checked yetcites [214] Parish T Schaeffer M Roberts G Duncan K HemZ is essential for heme biosynthesis in Mycobacterium tuberculosis Tuberculosis (Edinb) 85 2005 197 204 15850757 source
- Not checked yetcites [215] Tullius MV Harmston CA Owens CP Chim N Morse RP McMath LM Discovery and characterization of a unique mycobacterial heme acquisition system Proc Natl Acad Sci USA 108 2011 5051 5056 21383189 PMC3064333 source
- Not checked yetcites [216] Owens CP Chim N Goulding CW Insights on how the Mycobacterium tuberculosis heme uptake pathway can be used as a drug target Future Med Chem 5 2013 1391 1403 23919550 PMC3838433 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As the heme uptake, synthesis, and toxicity processes are well conserved and vital to bacterial pathogenesis”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Concluding Remarks
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“S. aureus Isd proteins have been the target of vaccine development with mixed success and monoclonal antibodies against IsdB have been studied for therapeutic use [209–213].”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > Current challenges and opportunities
What the sources say
- Not checked yetcites [209] Fowler VG Jr Proctor RA Where does a Staphylococcus aureus vaccine stand? Clin Microbiol Infect 20 5 2014 66 75 24476315 PMC4067250 source
- Not checked yetcites [210] Kuklin NA Clark DJ Secore S Cook J Cope LD McNeely T A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model Infect Immun 74 2006 2215 2223 16552052 PMC1418914 source
- Not checked yetcites [211] McNeely TB Shah NA Fridman A Joshi A Hartzel JS Keshari RS Mortality among recipients of the Merck V710 Staphylococcus aureus vaccine after postoperative S. aureus infections: an analysis of possible contributing host factors Hum Vaccin Immunother 10 2014 3513 3516 25483690 PMC4514053 source
- Not checked yetcites [212] Ebert T Smith S Pancari G Clark D Hampton R Secore S A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) with functional activity in vitro and in vivo Hum Antibodies 19 2010 113 128 21178283 source
- Not checked yetcites [213] Pancari G Fan H Smith S Joshi A Haimbach R Clark D Characterization of the mechanism of protection mediated by CS-D7, a monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) Front Cell Infect Microbiol 2 2012 36 22919628 PMC3417506 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Murine infection models are predictive of human bacterial pathogenesis.
“heme biosynthesis is vital to cause disease in murine models of infection”
The paper relies on this without support.
Transposon-sequencing and signature-tagged mutagenesis recovery defects indicate a gene's importance during infection.
“genes with marked mutations that are recovered at a lower frequency from the infected tissue relative to growth in vitro are considered important to infection”
The paper relies on this without support.
Animal models of H. influenzae infection reflect human pathogenesis.
“Several animal models have been used to demonstrate the role of heme uptake during H. influenzae infection.”
The paper relies on this without support.
Animal models of N. meningitidis meningitis reflect human virulence.
“HmbR is required for virulence in an infant rat model of meningitis [200].”
The paper relies on this without support.
In vitro heme utilization by H. influenzae reflects its in vivo infection biology.
“H. influenzae has evolved a variety of heme uptake systems important for growth in vitro using various host heme sources.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“If haemoglobin or haem is released from erythrocytes, it is rapidly bound by host haemoproteins, haptoglobin or haemopexin (HPX), further preventing Fe use by patho gens 13 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [13]
In the citing paper
“In addition to Fur‐mediated iron sensing, haem biosynthesis is also exquisitely regulated, with haem negatively regulating the activity of the rate‐limiting biosynthetic enzyme HemA. 85 , 86”
From The battle for iron in enteric infections (2020) · cites this paper as [86]
In the citing paper
“Gram-positive pathogenic bacteria, such as Staphylococcus aureus, Bacillus anthracis and Corynebacterium diphtheriae also rely on heme acquisition systems to establish infection (78).”
From Innate Nutritional Immunity (2018) · cites this paper as [78]
In the citing paper
“Heme acquisition is required for virulence in Staphylococcus aureus, B. anthracis, and Streptococcus pyogenes (27).”
From Transition Metals and Virulence in Bacteria (2016) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
“HpbA is another heme acquisition protein identified in nontypeable and type B H. influenzae.”
§ Heme Synthesis and Acquisition in Bacterial Pathogens > Gram-Negative Heme Acquisition Strategies > H. influenzae
“A lipoprotein, HbpA is important for growth using Hb, Hp–Hb, and heme-human serum albumin as heme sources [175,176].”
Citations
Cites
1 retracted
Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues
Cheng, A. G., Kim, H. K., Burts, M. L., Krausz, T., Schneewind, O., & Missiakas, D. M. (2009) · The FASEB Journal · doi:10.1096/fj.09-135467 · Cited by 437
RetractedThe Carbon Monoxide-binding Pigment of Liver Microsomes
Omura, T., & Sato, R. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)82244-3 · Cited by 11,781
Andrews, N. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412607 · Cited by 2,130
DNA damage and oxygen radical toxicity
Imlay, J. A., & Linn, S. (1988) · Science · doi:10.1126/science.3287616 · Cited by 1,974
Peters, J. W. (1998) · Science · doi:10.1126/science.282.5395.1853 · Cited by 1,891
Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro
Imlay, J. A., Chin, S. M., & Linn, S. (1988) · Science · doi:10.1126/science.2834821 · Cited by 1,555
Nutritional immunity: transition metals at the pathogen–host interface
Hood, M. I., & Skaar, E. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2836 · Cited by 1,535
Self-citationStructure, function, and formation of biological iron-sulfur clusters
Johnson, D. C., Dean, D. R., Smith, A. D., & Johnson, M. K. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133518 · Cited by 1,438
Iron in infection and immunity
Cassat, J. E., & Skaar, E. P. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.04.010 · Cited by 1,214
Self-citationProctor, R. A., von Eiff, C., Kahl, B. C., Becker, K., McNamara, P., Herrmann, M., & Peters, G. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1384 · Cited by 1,175
Cited by
Sorted by citations
Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701
Self-citationParamsothy, S., Nielsen, S. J., Kamm, M. A., Deshpande, N., Faith, J. J., Clemente, J. C., Paramsothy, R., Walsh, A. J., van den Bogaerde, J., Samuel, D., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.12.001 · Cited by 523
Transition Metals and Virulence in Bacteria
Palmer, L. D., & Skaar, E. P. (2016) · Annual Review of Genetics · doi:10.1146/annurev-genet-120215-035146 · Cited by 449
Self-citationDefining the core essential genome of Pseudomonas aeruginosa
Poulsen, B. E., Yang, R., Clatworthy, A. E., White, T. L., Osmulski, S. J., Li, L., Peñaranda, C., Lander, E. S., Shoresh, N., & Hung, D. T. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900570116 · Cited by 206
Handling heme: The mechanisms underlying the movement of heme within and between cells
Donegan, R. K., Moore, C. M., Hanna, D. A., & Reddi, A. R. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.005 · Cited by 155
Metadata
- Authors
- Choby, J. E., & Skaar, E. P.
- Affiliations
- Vanderbilt University (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Skaar, Eric P.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 428
- Issue
- 17
- Pages
- 3408-3428
- ISSN
- 0022-2836 (ISSN-L)
- PMC
- PMC5125930
- OpenAlex
- W2306188934
- Cited by
- 343
- References
- 258
- Citations by year
- 2026: 26 · 2025: 53 · 2024: 40 · 2023: 32 · 2022: 39 · 2021: 37 · 2020: 34 · 2019: 32 · 2018: 24 · 2017: 18 · 2016: 6
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (T32 GM065086, AI069233, AI073843)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Keywords
- heme biosynthesis, heme acquisition, pathogenic bacteria, hemoglobin, heme detoxification, iron acquisition, heme proteins, host-pathogen interaction, pathogenesis, electron transport chain
- MeSH terms
- Bacteria, Heme, Metabolic Networks and Pathways, Host-Pathogen Interactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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