The DOI matches its Crossref record; 252 of the 258 references it cites were found in a registry or an index; 31 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
269 Not checked yet · 48 Own interpretation · 11 No basis given · 9 Partly supported · 2 Not supported · 1 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 cited sources support only part of this claim — read each source’s verdict below.
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
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) states that protoporphyrinogen oxidase catalyzes the six-electron oxidation of protoporphyrinogen IX to protoporphyrin IX. The Discussion (page unavailable) describes different enzymes with this activity, but does not establish that there are exactly three; it says the enzyme's identity remains unknown in some Gram-negative organisms. (LLM, conf=0.86)
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) states that protoporphyrinogen IX is oxidized to protoporphyrin IX by protoporphyrinogen oxidase and identifies three unrelated enzymes that catalyze this step. It does not specify that the oxidation transfers six electrons; a search for “six-electron” and “six electrons” found no supporting passage. (LLM, conf=0.87)
- Partly supportedcites [50] Porra RJ Falk JE The enzymic conversion of coproporphyrinogen III into protoporphyrin IX Biochem J 90 1964 69 75 5832302 PMC1202522 sourceExperimental — accuracy not yet measured
The introduction (page not provided) describes protoporphyrinogen oxidase as oxidizing protoporphyrinogen IX to protoporphyrin IX, and the Discussion says the mitochondrial extract appears to contain that enzyme. The paper does not specify a six-electron oxidation or say that there are three protoporphyrinogen oxidase enzymes; it also treats the enzyme’s separate existence in its preparation as presumptive. (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.
- Partly supported
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.
Every source the paper cites for this claim was checked and supports it.
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
- Supportedcites [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
The Discussion (page not available) identifies hemin-receptor and hemoglobin-binding protein gene regions as more common in nontypeable H. influenzae otitis media isolates than in throat isolates. It suggests these regions may aid survival in the middle ear or represent virulence genes, supporting the claim's cautious wording. (LLM, conf=0.88)
- Supportedcites [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
The Introduction says NTHI heme acquisition genes may help determine virulence. The Abstract reports that several such genes were more prevalent in disease-causing than colonizing NTHI strains, supporting a potential role in virulence. This matches the claim’s cautious wording. (LLM, conf=0.94)
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.
- Supported
- 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.
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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
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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
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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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.
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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.
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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.
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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.
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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
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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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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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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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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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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.
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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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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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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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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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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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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.
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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
“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.
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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
“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.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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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.
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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.
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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.
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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 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.
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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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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.
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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.
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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.
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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.
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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.
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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.
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.
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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.
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.
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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
“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.
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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.
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.
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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.
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.
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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.
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.
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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
“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.
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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.
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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.
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]
In the citing paper
“Although host heme is sequestered in high‐affinity hemoproteins, bacterial pathogens must either synthesize heme or obtain it from the host during infection (Choby and Skaar 2016).”
From Nutritional Immunity in Wound Infection: Unveiling the Role of Dietary Elements in Host–Pathogen Interaction (2025) · cites this paper as Choby and Skaar 2016
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
Factors Determining the Susceptibility of Bacteria to Antibacterial Photodynamic Inactivation
Rapacka-Zdończyk, A., Woźniak, A., Michalska, K., Pierański, M. K., Ogonowska, P., Grinholc, M., & Nakonieczna, J. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.642609 · Cited by 135
Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens
Richard, K. L., Kelley, B. R., & Johnson, J. G. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00081 · Cited by 120
Lucidi, M., Visaggio, D., Migliaccio, A., Capecchi, G., Visca, P., Imperi, F., & Zarrilli, R. (2023) · Virulence · doi:10.1080/21505594.2023.2289769 · Cited by 130
Núñez, G., Sakamoto, K., & Soares, M. P. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800325 · Cited by 115
The Biochemical Landscape of Riboswitch Ligands
Breaker, R. R. (2022) · Biochemistry · doi:10.1021/acs.biochem.1c00765 · Cited by 120
Krishnan, A., Kloehn, J., Lunghi, M., Chiappino-Pepe, A., Waldman, B. S., Nicolas, D., Varesio, E., Hehl, A. B., Lourido, S., Vassily Hatzimanikatis, A., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.01.002 · Cited by 109
Triple threat: how diabetes results in worsened bacterial infections
Darwitz, B. P., Genito, C. J., & Thurlow, L. R. (2024) · Infection and Immunity · doi:10.1128/iai.00509-23 · Cited by 137
‘ARMAN’ archaea depend on association with euryarchaeal host in culture and in situ
Golyshina, O. V., Toshchakov, S. V., Makarova, K. S., Gavrilov, S. N., Korzhenkov, A. A., Cono, V. L., Arcadi, E., Nechitaylo, T. Y., Ferrer, M., Kublanov, I. V., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00104-7 · Cited by 108
PPE Surface Proteins Are Required for Heme Utilization by Mycobacterium tuberculosis
Mitra, A., Speer, A., Lin, K., Ehrt, S., & Niederweis, M. (2017) · mBio · doi:10.1128/mbio.01720-16 · Cited by 95
Iron Acquisition Mechanisms and Their Role in the Virulence of Burkholderia Species
Butt, A. T., & Thomas, M. S. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00460 · Cited by 103
In Vitro Detection of Porphyrin-Producing Wound Bacteria with Real-Time Fluorescence Imaging
Jones, L., Dunham, D., Rennie, M. Y., Kirman, J., López, A. J., Keim, K. C., Little, W., Gomez, A., Bourke, J., Ng, H., et al. (2020) · Future Microbiology · doi:10.2217/fmb-2019-0279 · Cited by 91
Heme and hemoglobin utilization by Mycobacterium tuberculosis
Mitra, A., Ko, Y.-H., Cingolani, G., & Niederweis, M. (2019) · Nature Communications · doi:10.1038/s41467-019-12109-5 · Cited by 81
Bacterial ABC transporters of iron containing compounds
Delepelaire, P. (2019) · Research in Microbiology · doi:10.1016/j.resmic.2019.10.008 · Cited by 84
Bilitewski, U., Blodgett, J. A. V., Duhme‐Klair, A., Dallavalle, S., Laschat, S., Routledge, A., & Schobert, R. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201701586 · Cited by 80
Law, S. K. K., & Tan, H. S. (2022) · Microbiological Research · doi:10.1016/j.micres.2022.127032 · Cited by 78
Sortases, Surface Proteins, and Their Roles in Staphylococcus aureus Disease and Vaccine Development
Schneewind, O., & Missiakas, D. M. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.psib-0004-2018 · Cited by 75
Microalgae and Bacteria Interaction—Evidence for Division of Diligence in the Alga Microbiota
Astafyeva, Y., Gurschke, M., Qi, M., Bergmann, L., Indenbirken, D., de Grahl, I., Katzowitsch, E., Reumann, S., Hanelt, D., Alawi, M., et al. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.00633-22 · Cited by 73
Lactic acid bacteria: Nature, characterization, mode of action, products and applications
Akpoghelie, P. O., Edo, G. I., Ali, A. B. M., Yousif, E., Zainulabdeen, K., Owheruo, J. O., Isoje, E. F., Igbuku, U. A., Essaghah, A. E. A., Makia, R. S., et al. (2025) · Process Biochemistry · doi:10.1016/j.procbio.2025.02.010 · Cited by 78
Bouzo, D., Cokcetin, N. N., Li, L., Ballerin, G., Bottomley, A. L., Lazenby, J., Whitchurch, C. B., Paulsen, I. T., Hassan, K. A., & Harry, E. J. (2020) · mSystems · doi:10.1128/msystems.00106-20 · Cited by 73
Porphyrin Production and Regulation in Cutaneous Propionibacteria
Barnard, E., Johnson, T., Ngo, T., Arora, U., Leuterio, G., McDowell, A., & Li, H. (2020) · mSphere · doi:10.1128/msphere.00793-19 · Cited by 70
Hadi, J. L., Wu, S., & Brightwell, G. (2020) · Foods · doi:10.3390/foods9121895 · Cited by 68
The elements of life: A biocentric tour of the periodic table
(2023) · Advances in Microbial Physiology · doi:10.1016/bs.ampbs.2022.11.001 · Cited by 71
Tuning the Binding Affinity of Heme-Responsive Biosensor for Precise and Dynamic Pathway Regulation
Zhang, J., Wang, Z., Su, T., Sun, H., Zhu, Y., Qi, Q., & Wang, Q. (2020) · iScience · doi:10.1016/j.isci.2020.101067 · Cited by 63
The battle for iron in enteric infections
Sousa Gerós, A., Simmons, A., Drakesmith, H., Aulicino, A., & Frost, J. N. (2020) · Immunology · doi:10.1111/imm.13236 · Cited by 58
Knippel, R. J., Wexler, A. G., Miller, J. M., Beavers, W. N., Weiss, A., de Crécy-Lagard, V., Edmonds, K. A., Giedroc, D. P., & Skaar, E. P. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.05.015 · Cited by 62
Self-citationThe synergistic effect of PDT and oxacillin on clinical isolates of Staphylococcus aureus
Iluz, N., Maor, ., Keller, N., & Malik, Z. (2018) · Lasers in Surgery and Medicine · doi:10.1002/lsm.22785 · Cited by 58
The convoluted history of haem biosynthesis
Kořený, L., Obornı́k, M., Horáková, E., Waller, R. F., & Lukeš, J. (2021) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12794 · Cited by 57
Wu, Y., Guo, S., Chen, F., Li, Y., Huang, Y., Liu, W., & Zhang, G. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011096 · Cited by 54
Leanse, L. G., Harrington, O. D., Fang, Y., Ahmed, I., Goh, X. S., & Dai, T. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02403 · Cited by 52
Antimicrobial Blue Light Inactivation of Microbial Isolates in Biofilms
Ferrer‐Espada, R., Wang, Y., Goh, X. S., & Dai, T. (2019) · Lasers in Surgery and Medicine · doi:10.1002/lsm.23159 · Cited by 52
de Oliveira, J., Denadai, M. B., & Costa, D. L. (2022) · Antioxidants · doi:10.3390/antiox11050861 · Cited by 54
Knippel, R. J., Zackular, J. P., Moore, J. L., Celis, A. I., Weiss, A., Washington, M. K., DuBois, J. L., Caprioli, R. M., & Skaar, E. P. (2018) · PLOS Pathogens · doi:10.1371/journal.ppat.1007486 · Cited by 46
Self-citationThe Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling
Osorio, C. P., Kanukuntla, T., Diaz, E. L., Jafri, N., Cummings, M., & Sfera, A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00143 · Cited by 50
Atto, B., Eapen, M. S., Sharma, P. K., Frey, U., Ammit, A. J., Markos, J., Chia, C., Larby, J., Haug, G., Weber, H. C., et al. (2019) · Clinical Science · doi:10.1042/cs20181009 · Cited by 49
Optical clearing of tissues: Issues of antimicrobial phototherapy and drug delivery
Tuchin, V. V., Genina, E. A., Tuchina, E. S., Svetlakova, A. V., & Svenskaya, Y. I. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114037 · Cited by 51
Metals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49
Mechanisms of host adaptation by bacterial pathogens
Barber, M. F., & Fitzgerald, J. R. (2024) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuae019 · Cited by 50
Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes
Gomes, A. C., Moreira, A. C., Mesquita, G., & Gomes, M. S. (2018) · Pharmaceuticals · doi:10.3390/ph11030084 · Cited by 52
Heme auxotrophy in abundant aquatic microbial lineages
Kim, S., Kang, I., Lee, J., Jeon, C. O., Giovannoni, S. J., & Cho, J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2102750118 · Cited by 46
Heme-iron acquisition in fungi
Roy, U., & Kornitzer, D. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.05.006 · Cited by 46
Jung, H.-J., Littmann, E. R., Seok, R., Leiner, I. M., Taur, Y., Peled, J. U., van den Brink, M. R. M., Ling, L., Chen, L., Kreiswirth, B. N., et al. (2019) · mBio · doi:10.1128/mbio.02663-18 · Cited by 52
Metabolic network percolation quantifies biosynthetic capabilities across the human oral microbiome
Bernstein, D. B., Dewhirst, F. E., & Segrè, D. (2019) · eLife · doi:10.7554/elife.39733 · Cited by 44
Wang, M., Nie, Y., & Wu, X. (2020) · The ISME Journal · doi:10.1038/s41396-020-00800-1 · Cited by 42
López, A. J., Jones, L., Reynolds, L., Diaz, R. C., George, I. K., Little, W., Fleming, D. F., D’souza, A., Rennie, M. Y., Rumbaugh, K. P., et al. (2021) · International Wound Journal · doi:10.1111/iwj.13564 · Cited by 44
Bateman, T. J., Shah, M., Ho, T. P., Shin, H. E., Pan, C., Harris, G., Fegan, J. E., Islam, E. A., Ahn, S. K., Hooda, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26545-9 · Cited by 44
Fungal physiology: Robbing the bank of haem iron
Philpott, C. C., & Protchenko, O. V. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.179 · Cited by 42
Favre, L., Ortalo-Magné, A., Pichereaux, C., Gargaros, A., Burlet‐Schiltz, O., Cotelle, V., & Culioli, G. (2018) · Biofouling · doi:10.1080/08927014.2017.1413551 · Cited by 42
Mollaeva, M. R., Yabbarov, N. G., Sokol, M. B., Chirkina, M., Mollaev, M. D., Zabolotskii, A. I., Seregina, I. F., Bolshov, M. A., Kaplun, A. P., & Nikolskaya, E. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212261 · Cited by 40
Human Serum Albumin Facilitates Heme-Iron Utilization by Fungi
Pinsky, M., Roy, U., Moshe, S., Weissman, Z., & Kornitzer, D. (2020) · mBio · doi:10.1128/mbio.00607-20 · Cited by 40
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Sauceda, C., Bayne, C. F., Sudqi, K., González, A., Dulai, P. S., Knight, R. D., Gonzalez, D. J., & Gonzalez, C. G. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2154092 · Cited by 40
Wang, Y., Ferrer‐Espada, R., Baglo, Y., Goh, X. S., Held, K. D., Grad, Y. H., Gu, Y., Gelfand, J. A., & Dai, T. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz018 · Cited by 37
Celis, A. I., & Relman, D. A. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.032 · Cited by 34
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Iskandar, C. F., Borges, F., Taminiau, B., Daube, G., Zagorec, M., Remenant, B., Leisner, J. J., Hansen, M. A., Sørensen, S. J., Mangavel, C., et al. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00357 · Cited by 39
Gut Microbiome Alterations Associated with Diabetes in Mexican Americans in South Texas
Kwan, S., Sabotta, C. M., Joon, A. Y., Wei, P., Petty, L. E., Below, J. E., Wu, X., Zhang, J., Jenq, R. R., Hawk, E. T., et al. (2022) · mSystems · doi:10.1128/msystems.00033-22 · Cited by 37
Haley, K. P., & Gaddy, J. A. (2016) · Gastroenterology Research and Practice · doi:10.1155/2016/3019362 · Cited by 35
Genomic erosion and extensive horizontal gene transfer in gut-associated Acetobacteraceae
Brown, B. P., & Wernegreen, J. J. (2019) · BMC Genomics · doi:10.1186/s12864-019-5844-5 · Cited by 35
Wittwer, M., Altpeter, E., Pilo, P., Gygli, S. M., Beuret, C. M., Foucault, F., Ackermann‐Gäumann, R., Karrer, U., Jacob, D., Grunow, R., et al. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00089 · Cited by 35
Shi, Y.-J., Fang, Q., Huang, H., Gong, C., & Hu, Y. (2019) · Veterinary Research · doi:10.1186/s13567-019-0693-4 · Cited by 34
Gianquinto, E., Moscetti, I., Bei, O. D., Campanini, B., Marchetti, M., Luque, F. J., Cannistraro, S., Ronda, L., Bizzarri, A. R., Spyrakis, F., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54970-w · Cited by 31
Lena, A., Marino, M., Manzano, M., Comuzzi, C., & Maifreni, M. (2023) · Food Engineering Reviews · doi:10.1007/s12393-023-09355-1 · Cited by 35
Structural and functional diversity of transient heme binding to bacterial proteins
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Rodríguez-Arce, I., Al-Jubair, T., Euba, B., Fernández-Calvet, A., Gil-Campillo, C., Martí, S., Törnroth‐Horsefield, S., Riesbeck, K., & Garmendia, J. (2019) · Virulence · doi:10.1080/21505594.2019.1596506 · Cited by 31
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Hofbauer, S., Helm, J., Obinger, C., Djinović‐Carugo, K., & Furtmüller, P. G. (2019) · FEBS Journal · doi:10.1111/febs.15164 · Cited by 30
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Brown, J. B., Lee, M. A., & Smith, A. T. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00586 · Cited by 31
Quadros, H. C., Silva, M. C. B., & Moreira, D. R. M. (2022) · Pharmaceuticals · doi:10.3390/ph15010060 · Cited by 33
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Self-citationdos Santos, P. T., Menendez-Gil, P., Sabharwal, D., Christensen, J.-H., Brunhede, M. Z., Lillebæk, E. M. S., & Kallipolitis, B. H. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00599 · Cited by 31
Bennett, M. R., Bombardi, R. G., Kose, N., Parrish, E. H., Nagel, M. B., Petit, R. A., Read, T. D., Schey, K. L., Thomsen, I. P., Skaar, E. P., et al. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiy635 · Cited by 29
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Dettman, J. R., & Kassen, R. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msaa226 · Cited by 30
Lennon, Á. M., Brune, L., Techert, S., & Buchalla, W. (2022) · Caries Research · doi:10.1159/000528731 · Cited by 28
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Elbediwi, M., & Rolff, J. (2024) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkae128 · Cited by 28
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Sy, B. M., & Tree, J. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.622202 · Cited by 21
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Beas, J. Z., Videira, M. A. M., & Saraiva, L. M. (2021) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2021.214286 · Cited by 27
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Schwiesow, L., Mettert, E. L., Wei, Y., Miller, H. K., Herrera, N. G., Balderas, D., Kiley, P. J., & Auerbuch, V. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00047 · Cited by 28
Śmiga, M., & Olczak, T. (2025) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf019 · Cited by 30
Videira, M. A. M., Lobo, S. A. L., Silva, L. S. O., Palmer, D. J., Warren, M. J., PRIETO, M. J. E., Coutinho, A., Filipa L. Sousa, Fernandes, F., & Saraiva, L. M. (2018) · Molecular Microbiology · doi:10.1111/mmi.14060 · Cited by 26
Walter, A. B., Simpson, J., Jenkins, J. L., Skaar, E. P., & Jansen, D. (2019) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2019.101624 · Cited by 27
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Flannagan, R. S., Farrell, T. J., Trothen, S. M., Dikeakos, J. D., & Heinrichs, D. E. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020002833 · Cited by 31
Nakamura, H., Hisano, T., Rahman, M., Tosha, T., Shirouzu, M., & Shiro, Y. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2123385119 · Cited by 26
Zheng, Y., He, D., Zuo, W., Wang, W., Wu, K., Wu, H., Yuan, Y., Huang, Y.-J., Li, H., Lu, Y., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105738 · Cited by 31
Antibacterial photosensitization through activation of coproporphyrinogen oxidase
Surdel, M. C., Horvath, D. J., Lojek, L. J., Fullen, A. R., Simpson, J., Dutter, B. F., Salleng, K. J., Ford, J. B., Jenkins, J. L., Raju, N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700469114 · Cited by 26
Self-citationJoshi, C., Patel, P., Palep, H., & Kothari, V. (2019) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-019-2428-5 · Cited by 24
Luthra, A., Montezuma-Rusca, J. M., Vake, C. J. L., LeDoyt, M., Delgado, K. N., Davenport, T. C., Fiel-Gan, M. D., Caimano, M. J., Radolf, J. D., & Hawley, K. L. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008871 · Cited by 25
Weissman, Z., Pinsky, M., Donegan, R. K., Reddi, A. R., & Kornitzer, D. (2021) · Cellular Microbiology · doi:10.1111/cmi.13282 · Cited by 26
Brunson, D. N., Colomer‐Winter, C., Lam, L. N., & Lemos, J. A. C. (2023) · Infection and Immunity · doi:10.1128/iai.00496-22 · Cited by 25
Weissman, Z., Pinsky, M., Donegan, R. K., Reddi, A. R., & Kornitzer, D. (2020) · doi:10.1101/2020.07.26.221606 · Cited by 26
Calder, A., Menkiti, C. J., Çağdaş, A., Santos, J. L., Streich, R., Wong, A., Avini, A. H., Bojang, E., Yogamanoharan, K., Sivanesan, N., et al. (2020) · Microbial Genomics · doi:10.1099/mgen.0.000423 · Cited by 25
Leveraging host-genetics and gut microbiota to determine immunocompetence in pigs
Ramayo‐Caldas, Y., Zingaretti, L. M., Pérez-Pascual, D., Alexandre, P. A., Reverter, A., Dalmau, A., Quintanilla, R., & Ballester, M. (2021) · Animal Microbiome · doi:10.1186/s42523-021-00138-9 · Cited by 25
Michalska, K., Rychłowski, M., Krupińska, M., Szewczyk, G. M., Sarna, T., & Nakonieczna, J. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.1c00993 · Cited by 24
Sato, T., Nonoyama, S., Kimura, A., Nagata, Y., Ohtsubo, Y., & Tsuda, M. (2017) · Applied and Environmental Microbiology · doi:10.1128/aem.00479-17 · Cited by 25
Zhang, Y., Zhao, L., Chen, W., Huang, Y., Yang, L., Sarathbabu, V., Wu, Z., Li, J., Nie, P., & Lin, L. (2017) · Microbial Pathogenesis · doi:10.1016/j.micpath.2017.08.035 · Cited by 25
Zhang, J., Liang, Q., Mu, D., Lian, F.-B., Gong, Y., Ye, M., Chen, G., Ye, Y.-Q., & Du, Z. (2024) · mLife · doi:10.1002/mlf2.12093 · Cited by 24
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.
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