The DOI matches its Crossref record; 232 of the 235 references it cites were found in a registry or an index, and 3 are not checked yet; 9 of the 213 sources its claims cite were checked for support.
Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity
Open accessAbstract
Transition metals are essential nutrients to virtually all forms of life, including bacterial pathogens. In Staphylococcus aureus, metal ions participate in diverse biochemical processes such as metabolism, DNA synthesis, regulation of virulence factors, and defense against oxidative stress. As an innate immune response to bacterial infection, vertebrate hosts sequester transition metals in a process that has been termed "nutritional immunity." To successfully infect vertebrates, S. aureus must overcome host sequestration of these critical nutrients. The objective of this review is to outline the current knowledge of staphylococcal metal ion acquisition systems, as well as to define the host mechanisms of nutritional immunity during staphylococcal infection.
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137 Not checked yet · 41 Own interpretation · 5 No basis given · 3 Partly supported · 2 Supported · 2 Supported so far · 1 Own result · accuracy not yet measured
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In the paper
“S. aureus also has the capability to utilize mammalian catecholamine hormones as an iron source.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Supportedcites [60] Beasley FC, Marolda CL, Cheung J, Buac S, Heinrichs DE (2011) Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by staphyloferrin a, staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79(6):2345–2355. doi:10.1128/IAI.00117-11 source
The Results report that mammalian catecholamine hormones enhanced growth of staphyloferrin-deficient S. aureus in human serum or with human transferrin. The Discussion identifies SstABCD-mediated uptake of iron liberated from transferrin by catecholamines. The study did not observe additional growth enhancement in wild-type S. aureus under the tested conditions, but it establishes the claimed capability. (LLM, conf=0.91)
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In the paper
“Once heme enters the staphylococcal cytoplasm, the tetrapyrrole ring is degraded to liberate free iron by two heme-oxygenases, IsdG and IsdI (Fig. 1) [102, 103].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [102] Skaar EP, Gaspar AH, Schneewind O (2004) IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus. J Biol Chem 279(1):436–443. doi:10.1074/jbc.M307952200 source
- Supportedcites [103] Wu R, Skaar EP, Zhang R, Joachimiak G, Gornicki P, Schneewind O, Joachimiak A (2005) Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural similarity to monooxygenases. J Biol Chem 280(4):2840–2846. doi:10.1074/jbc.M409526200 source
The Abstract states that heme in the staphylococcal cytoplasm can be degraded to release iron and that purified IsdG and IsdI cleave the heme tetrapyrrole ring. It also notes that some cytoplasmic heme is incorporated into bacterial heme proteins instead. (LLM, conf=0.92)
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In the paper
“Inactivation of alpha-hemolysin limits the virulence of S. aureus [108–114].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Supportedcites [108] Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, DeLeo FR (2010) Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 202(7):1050–1058. doi:10.1086/656043 source
In Results (‘Expression of hla enhances virulence in skin and soft-tissue infections’), mice infected with an alpha-hemolysin–deficient USA300 strain had significantly smaller lesions than mice infected with the wild-type strain. Alpha-hemolysin–deficient USA300 and Newman strains also caused little or no dermonecrosis. The evidence concerns virulence in a mouse skin-infection model, not every form of S. aureus infection. (LLM, conf=0.90)
- Not checked yetcites [109] Bubeck Wardenburg J, Patel RJ, Schneewind O (2007) Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect Immun 75(2):1040–1044. doi:10.1128/IAI.01313-06 source
- Not checked yetcites [110] Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O (2007) Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med 13(12):1405–1406. doi:10.1038/nm1207-1405 source
- Not checked yetcites [111] Ji Y, Marra A, Rosenberg M, Woodnutt G (1999) Regulated antisense RNA eliminates alpha-toxin virulence in Staphylococcus aureus infection. J Bacteriol 181(21):6585–6590 source
- Not checked yetcites [112] Kernodle DS, Voladri RK, Menzies BE, Hager CC, Edwards KM (1997) Expression of an antisense hla fragment in Staphylococcus aureus reduces alpha-toxin production in vitro and attenuates lethal activity in a murine model. Infect Immun 65(1):179–184 source
- Not checked yetcites [113] Callegan MC, Engel LS, Hill JM, O’Callaghan RJ (1994) Corneal virulence of Staphylococcus aureus: roles of alpha-toxin and protein A in pathogenesis. Infect Immun 62(6):2478–2482 source
- Not checked yetcites [114] Patel AH, Nowlan P, Weavers ED, Foster T (1987) Virulence of protein A-deficient and alpha-toxin-deficient mutants of Staphylococcus aureus isolated by allele replacement. Infect Immun 55(12):3103–3110 source
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In the paper
“Deletion of mntR leads to constitutive transcription of mntABC irrespective of manganese levels.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Supportedcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
The section “MntR mediates regulation of mntABC and mntH by Mn(II)” reports constitutive mntABC transcription in the mntR mutant at every manganese concentration tested, while transcription in wild-type cells was repressed as manganese increased. This supports the claim within the tested manganese range. (LLM, conf=0.95)
- Partly supportedcites [145] Horsburgh MJ, Clements MO, Crossley H, Ingham E, Foster SJ (2001) PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. Infect Immun 69(6):3744–3754. doi:10.1128/IAI.69.6.3744-3754.2001 sourceExperimental — accuracy not yet measured
The Discussion describes MntR as a regulator of manganese uptake transporters, including MntABC, and the introductory passage describes manganese-dependent regulation of the related mntABCD operon. The Results show transcription remaining unrepressed by manganese in a perR mutant, not an mntR deletion. Our copy does not establish constitutive mntABC transcription after mntR deletion. (LLM, conf=0.82)
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In the paper
“In addition to regulation by MntR, mntABC is negatively regulated by PerR, a manganese and iron-dependent Fur homologue that controls responses to oxidative stress [144, 145].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Partly supportedcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 sourceExperimental — accuracy not yet measured
The “Regulation of mntABC by PerR” section reports incomplete repression in a perR mutant, supporting negative regulation of mntABC. The Introduction identifies PerR as a Fur homologue involved in peroxide-stress responses, but describes S. aureus PerR as manganese-dependent; it assigns manganese-and-iron dependence to B. subtilis PerR. The iron-dependent description is therefore not supported for the S. aureus PerR studied here. Page numbers were not provided for these passages. (LLM, conf=0.88)
- Partly supportedcites [145] Horsburgh MJ, Clements MO, Crossley H, Ingham E, Foster SJ (2001) PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. Infect Immun 69(6):3744–3754. doi:10.1128/IAI.69.6.3744-3754.2001 sourceExperimental — accuracy not yet measured
The paper identifies PerR as a Fur homologue that represses oxidative-stress genes in S. aureus. But the Discussion says a regulatory link between the PerR and MntR regulons had not been reported and treats such a link as hypothetical; it does not support the claim that PerR negatively regulates mntABC. (LLM, conf=0.88)
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In the paper
“Similarly, orthopedic implants made of a titanium-copper alloy are antibacterial in a rabbit model of staphylococcal implant-associated infection [225].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Partly supportedcites [225] Shirai T, Tsuchiya H, Shimizu T, Ohtani K, Zen Y, Tomita K (2009) Prevention of pin tract infection with titanium-copper alloys. J Biomed Mater Res B Appl Biomater 91(1):373–380. doi:10.1002/jbm.b.31412 sourceExperimental — accuracy not yet measured
The In vitro antimicrobial properties section reports testing titanium–copper implants against S. aureus, and the Discussion reports antibacterial activity from the combined in vitro and in vivo results. The rabbit study examined pin-tract inflammation and infection, but our copy does not establish that the rabbits had a staphylococcal implant-associated infection; the named S. aureus exposure was in vitro. (LLM, conf=0.88)
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In the paper
“The most well characterized example of nutritional immunity during staphylococcal infection is iron sequestration, in which iron is maintained predominantly intracellularly or in complex with high-affinity host binding proteins [32].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Introduction
What the sources say
- Not checked yetcites [32] Weinberg ED (2009) Iron availability and infection. Biochim Biophys Acta 1790(7):600–605. doi:10.1016/j.bbagen.2008.07.002 source
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In the paper
“Emerging evidence suggests that the principle of nutritional immunity extends to other transition metals, including zinc and manganese [34].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Introduction
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
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In the paper
“Since iron is necessary for bacterial proliferation, S. aureus must circumvent iron sequestration in order to successfully infect host tissues.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Introduction
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- Rests on an assumption: Iron is necessary for bacterial proliferation.
In the paper
“The result of this sequestration is an extracellular iron concentration insufficient to support bacterial growth [33].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Introduction
What the sources say
- Not checked yetcites [33] Braun V, Hantke K, Koster W (1998) Bacterial iron transport: mechanisms, genetics, and regulation. Met Ions Biol Syst 35:67–145
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In the paper
“Accordingly, staphylococci have evolved systems for the acquisition, processing, and detoxification of iron and iron-containing host molecules and proteins.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Introduction
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In the paper
“Heme is the major iron reservoir in vertebrates, accounting for up to 80% of total body iron [38].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host
What the sources say
- Not checked yetcites [38] Crichton R (2001) Inorganic biochemistry of iron metabolism: from molecular mechanisms to clinical consequences, vol 2. Wiley, West Sussex source
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In the paper
“To successfully infect humans, S. aureus utilizes siderophores and a heme acquisition system to overcome host iron sequestration (Fig. 1).”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“S. aureus produces two polycarboxylate-type siderophores, staphyloferrin A and staphyloferrin B, which were initially isolated and characterized from Staphylococcus hyicus [45].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [45] Meiwes J, Fiedler HP, Haag H, Zahner H, Konetschny-Rapp S, Jung G (1990) Isolation and characterization of staphyloferrin A, a compound with siderophore activity from Staphylococcus hyicus DSM 20459. FEMS Microbiol Lett 55(1–2):201–205 source
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In the paper
“Iron acquisition by staphyloferrin A and staphyloferrin B is regulated by the ferric uptake regulator (Fur) in response to environmental iron concentrations [47–49].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [47] Beasley FC, Vines ED, Grigg JC, Zheng Q, Liu S, Lajoie GA, Murphy ME, Heinrichs DE (2009) Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus. Mol Microbiol 72(4):947–963. doi:10.1111/j.1365-2958.2009.06698.x source
- Not checked yetcites [48] Friedman DB, Stauff DL, Pishchany G, Whitwell CW, Torres VJ, Skaar EP (2006) Staphylococcus aureus redirects central metabolism to increase iron availability. PLoS Pathog 2(8):e87. doi:10.1371/journal.ppat.0020087 source
- Not checked yetcites [49] Horsburgh MJ, Ingham E, Foster SJ (2001) In Staphylococcus aureus, Fur is an interactive regulator with PerR, contributes to virulence, and is necessary for oxidative stress resistance through positive regulation of catalase and iron homeostasis. J Bacteriol 183(2):468–475. doi:10.1128/JB.183.2.468-475.2001 source
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, S. aureus preferentially imports heme-iron over transferrin-iron.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
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In the paper
“Siderocalin binds enterobactin, a catecholate siderophore produced by E. coli, resulting in bacteriostasis in iron-limited conditions [75, 76].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
What the sources say
- Not checked yetcites [75] Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10(5):1033–1043 source
- Not checked yetcites [76] Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432(7019):917–921. doi:10.1038/nature03104 source
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In the paper
“Collectively, these results suggest that siderophore-mediated iron acquisition is important for S. aureus virulence.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
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In the paper
“Yet both staphyloferrin A and staphyloferrin B can remove iron from human holotransferrin to support S. aureus growth in iron-deplete conditions [60].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [60] Beasley FC, Marolda CL, Cheung J, Buac S, Heinrichs DE (2011) Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by staphyloferrin a, staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79(6):2345–2355. doi:10.1128/IAI.00117-11 source
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In the paper
“Thus, production of siderocalin is a host strategy to sequester iron that has been earmarked for bacterial utilization.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
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In the paper
“When S. aureus is grown in the presence of isotopically labeled iron complexed to either transferrin or heme, a fourfold to fivefold enrichment in the ratio of heme-iron to transferrin-iron is noted in bacteria as compared with the media [54].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [54] Skaar EP, Humayun M, Bae T, DeBord KL, Schneewind O (2004) Iron-source preference of Staphylococcus aureus infections. Science 305(5690):1626–1628. doi:10.1126/science.1099930 source
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In the paper
“Brock and Ng demonstrated that S. aureus is capable of utilizing the hydroxymate-type siderophore desferrioxamine as an iron source [61].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [61] Brock JH, Ng J (1983) The effect of desferrioxamine on the growth of Staphylococcus aureus, Yersinia enterocolitica and Streptococcus faecalis in human serum: uptake of desferrioxamine-bound iron. FEMS Microbiol Lett 20(3):439–442 source
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In the paper
“Mutation of the loci encoding staphyloferrin A or staphyloferrin B alone does not lead to a statistically significant reduction in colony recovery from the organs of intravenously infected mice.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
What the sources say
- Not checked yetcites [60] Beasley FC, Marolda CL, Cheung J, Buac S, Heinrichs DE (2011) Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by staphyloferrin a, staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79(6):2345–2355. doi:10.1128/IAI.00117-11 source
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In the paper
“Inactivation of these genes, designated heme-regulated transporter genes hrtA and hrtB, severely impairs the ability of S. aureus to grow on high concentrations of heme.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [106] Torres VJ, Stauff DL, Pishchany G, Bezbradica JS, Gordy LE, Iturregui J, Anderson KL, Dunman PM, Joyce S, Skaar EP (2007) A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe 1(2):109–119. doi:10.1016/j.chom.2007.03.001 source
- Not checked yetcites [107] Stauff DL, Bagaley D, Torres VJ, Joyce R, Anderson KL, Kuechenmeister L, Dunman PM, Skaar EP (2008) Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response. J Bacteriol 190(10):3588–3596. doi:10.1128/JB.01921-07 source
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In the paper
“Staphylococci exposed to subinhibitory concentrations of heme can subsequently resist heme toxicity at lethal concentrations, suggesting an adaptive response to exogenous heme [106].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [106] Torres VJ, Stauff DL, Pishchany G, Bezbradica JS, Gordy LE, Iturregui J, Anderson KL, Dunman PM, Joyce S, Skaar EP (2007) A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe 1(2):109–119. doi:10.1016/j.chom.2007.03.001 source
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In the paper
“The Isd system is encoded by ten genes in five operons: isdA, isdB, isdCDEFsrtBisdG, isdH, and orfXisdI [95].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [95] Hammer ND, Skaar EP (2011) Molecular mechanisms of Staphylococcus aureus iron acquisition. Annu Rev Microbiol. doi:10.1146/annurev-micro-090110-102851 source
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In the paper
“These and subsequent experiments suggest that HrtAB is a transport system dedicated to the excretion of excess heme or a toxic heme metabolite [106, 107].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [106] Torres VJ, Stauff DL, Pishchany G, Bezbradica JS, Gordy LE, Iturregui J, Anderson KL, Dunman PM, Joyce S, Skaar EP (2007) A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe 1(2):109–119. doi:10.1016/j.chom.2007.03.001 source
- Not checked yetcites [107] Stauff DL, Bagaley D, Torres VJ, Joyce R, Anderson KL, Kuechenmeister L, Dunman PM, Skaar EP (2008) Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response. J Bacteriol 190(10):3588–3596. doi:10.1128/JB.01921-07 source
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In the paper
“In S. aureus, heme acquisition is mediated by the iron-regulated surface determinant (Isd) system.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [95] Hammer ND, Skaar EP (2011) Molecular mechanisms of Staphylococcus aureus iron acquisition. Annu Rev Microbiol. doi:10.1146/annurev-micro-090110-102851 source
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In the paper
“These findings suggested a model whereby S. aureus can fine-tune its capacity for heme utilization based on the environmental conditions encountered.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
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In the paper
“Several lines of evidence indicate that disruption of the Isd heme acquisition system at each step (surface receptor binding, transport across the cell wall, transport across the cell membrane, or release of iron from heme) leads to decreased virulence in animal models of staphylococcal infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [96] Torres VJ, Pishchany G, Humayun M, Schneewind O, Skaar EP (2006) Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization. J Bacteriol 188(24):8421–8429. doi:10.1128/JB.01335-06 source
- Not checked yetcites [116] Cheng AG, Kim HK, Burts ML, Krausz T, Schneewind O, Missiakas DM (2009) Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J 23(10):3393–3404. doi:10.1096/fj.09-135467 source
- Not checked yetcites [117] Kim HK, DeDent A, Cheng AG, McAdow M, Bagnoli F, Missiakas DM, Schneewind O (2010) IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge. Vaccine 28(38):6382–6392. doi:10.1016/j.vaccine.2010.02.097 source
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In the paper
“The ability of staphylococci to acquire heme and hemoproteins in vivo is facilitated by lysis of host erythrocytes by pore-forming toxins such as alpha-hemolysin (encoded by hla) (Fig. 1).”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [108] Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, DeLeo FR (2010) Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 202(7):1050–1058. doi:10.1086/656043 source
- Not checked yetcites [109] Bubeck Wardenburg J, Patel RJ, Schneewind O (2007) Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect Immun 75(2):1040–1044. doi:10.1128/IAI.01313-06 source
- Not checked yetcites [110] Bubeck Wardenburg J, Bae T, Otto M, Deleo FR, Schneewind O (2007) Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat Med 13(12):1405–1406. doi:10.1038/nm1207-1405 source
- Not checked yetcites [111] Ji Y, Marra A, Rosenberg M, Woodnutt G (1999) Regulated antisense RNA eliminates alpha-toxin virulence in Staphylococcus aureus infection. J Bacteriol 181(21):6585–6590 source
- Not checked yetcites [112] Kernodle DS, Voladri RK, Menzies BE, Hager CC, Edwards KM (1997) Expression of an antisense hla fragment in Staphylococcus aureus reduces alpha-toxin production in vitro and attenuates lethal activity in a murine model. Infect Immun 65(1):179–184 source
- Not checked yetcites [113] Callegan MC, Engel LS, Hill JM, O’Callaghan RJ (1994) Corneal virulence of Staphylococcus aureus: roles of alpha-toxin and protein A in pathogenesis. Infect Immun 62(6):2478–2482 source
- Not checked yetcites [114] Patel AH, Nowlan P, Weavers ED, Foster T (1987) Virulence of protein A-deficient and alpha-toxin-deficient mutants of Staphylococcus aureus isolated by allele replacement. Infect Immun 55(12):3103–3110 source
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In the paper
“Finally, IsdA protects against the bactericidal activity of lactoferrin [130].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [130] Clarke SR, Foster SJ (2008) IsdA protects Staphylococcus aureus against the bactericidal protease activity of apolactoferrin. Infect Immun 76(4):1518–1526. doi:10.1128/IAI.01530-07 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Collectively, these results suggest an important role for surface proteins of the Isd system in staphylococcal virulence, and have led to additional experiments investigating the vaccine potential of these proteins.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
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In the paper
“Mutation of isdA, isdB, and isdC, but not isdH, decreases bacterial recovery and organ abscesses in murine models of systemic infection [96, 116, 117].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [96] Torres VJ, Pishchany G, Humayun M, Schneewind O, Skaar EP (2006) Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization. J Bacteriol 188(24):8421–8429. doi:10.1128/JB.01335-06 source
- Not checked yetcites [116] Cheng AG, Kim HK, Burts ML, Krausz T, Schneewind O, Missiakas DM (2009) Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J 23(10):3393–3404. doi:10.1096/fj.09-135467 source
- Not checked yetcites [117] Kim HK, DeDent A, Cheng AG, McAdow M, Bagnoli F, Missiakas DM, Schneewind O (2010) IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge. Vaccine 28(38):6382–6392. doi:10.1016/j.vaccine.2010.02.097 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, the contribution of IsdA to staphylococcal virulence may extend beyond its role in heme acquisition.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
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In the paper
“However, sequestration of manganese is also an important facet of the innate immune response to staphylococcal infection [34].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
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In the paper
“Manganese-dependent bacterial enzymes are necessary for myriad processes, including carbohydrate and amino acid metabolism, signal transduction, stringent response, and defense against oxidative stress [136].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection
What the sources say
- Not checked yetcites [136] Jakubovics NS, Jenkinson HF (2001) Out of the iron age: new insights into the critical role of manganese homeostasis in bacteria. Microbiology 147(Pt 7):1709–1718 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Manganese is an essential nutrient for both eukaryotic and prokaryotic organisms.
In the paper
“In contrast, mutation of isdG, but not isdI, results in decreased recovery from infected kidneys [105].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [105] Reniere ML, Skaar EP (2008) Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem. Mol Microbiol 69(5):1304–1315. doi:10.1111/j.1365-2958.2008.06363.x source
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In the paper
“The mechanism by which mutation of hssR leads to immunomodulation remains to be characterized, but disruption of heme sensing and detoxification systems clearly impact staphylococcal pathogenesis.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
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In the paper
“Mutation of either isdI or isdG results in decreased colony recovery from the hearts of systemically infected mice.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [105] Reniere ML, Skaar EP (2008) Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem. Mol Microbiol 69(5):1304–1315. doi:10.1111/j.1365-2958.2008.06363.x source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Heme transport across the cell membrane is also required for staphylococcal virulence.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, concurrent inactivation of htsA and isdE leads to a statistically significant decrease in bacterial burden in the lung, heart and kidneys of systemically infected mice [131].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [131] Mason WJ, Skaar EP (2009) Assessing the contribution of heme-iron acquisition to Staphylococcus aureus pneumonia using computed tomography. PLoS One 4(8):e6668. doi:10.1371/journal.pone.0006668 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This hepatic hypervirulence is the result of inhibition of a liver-specific immune response.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further experiments revealed that inactivation of HrtA leads to membrane damage which triggers increased expression and secretion of immunomodulatory factors [132].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [132] Attia AS, Benson MA, Stauff DL, Torres VJ, Skaar EP (2010) Membrane damage elicits an immunomodulatory program in Staphylococcus aureus. PLoS Pathog 6(3):e1000802. doi:10.1371/journal.ppat.1000802 source
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In the paper
“Rather than compromising virulence, S. aureus strains possessing mutations in hrtA or hssR grow to an average of two to three logs higher bacterial density in the livers of infected mice as compared with wild-type staphylococci [106].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [106] Torres VJ, Stauff DL, Pishchany G, Bezbradica JS, Gordy LE, Iturregui J, Anderson KL, Dunman PM, Joyce S, Skaar EP (2007) A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe 1(2):109–119. doi:10.1016/j.chom.2007.03.001 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, mntH transcription is reduced in the absence of MntR”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [138] Que Q, Helmann JD (2000) Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins. Mol Microbiol 35(6):1454–1468 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, the success of bacterial pathogens in human infection depends on the ability to obtain this critical nutrient from host tissues.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Manganese is an essential nutrient for both eukaryotic and prokaryotic organisms.
None of the sources cited for this claim have been checked yet.
In the paper
“In manganese-replete conditions, transcription of mntABC is repressed by MntR.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
- Not checked yetcites [145] Horsburgh MJ, Clements MO, Crossley H, Ingham E, Foster SJ (2001) PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. Infect Immun 69(6):3744–3754. doi:10.1128/IAI.69.6.3744-3754.2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The transcriptional regulator MntR affects expression of both mntABC and mntH.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
- Not checked yetcites [145] Horsburgh MJ, Clements MO, Crossley H, Ingham E, Foster SJ (2001) PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. Infect Immun 69(6):3744–3754. doi:10.1128/IAI.69.6.3744-3754.2001 source
- Not checked yetcites [138] Que Q, Helmann JD (2000) Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins. Mol Microbiol 35(6):1454–1468 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
“Likewise, prevention or resolution of infection is aided by host mechanisms that sequester manganese from invading pathogens.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that MntR may be a bifunctional regulator in S. aureus, as previously described for B. subtilis [138].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [138] Que Q, Helmann JD (2000) Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins. Mol Microbiol 35(6):1454–1468 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that MntABC may be the dominant manganese transporter in S. aureus under in vitro conditions [144].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, mutation of mntH does not lead to an appreciable growth defect in metal-depleted media”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The activities of SodA and SodM are dependent on manganese [148, 149].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [148] Clements MO, Watson SP, Foster SJ (1999) Characterization of the major superoxide dismutase of Staphylococcus aureus and its role in starvation survival, stress resistance, and pathogenicity. J Bacteriol 181(13):3898–3903 source
- Not checked yetcites [149] Valderas MW, Hart ME (2001) Identification and characterization of a second superoxide dismutase gene (sodM) from Staphylococcus aureus. J Bacteriol 183(11):3399–3407. doi:10.1128/JB.183.11.3399-3407.2001 source
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In the paper
“Aerobically growing microorganisms are at risk for toxicity from reactive oxygen species, and staphylococcal manganese acquisition is crucial for defense against oxidative stress.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Several other pathogens also require manganese uptake for infection, including Enterococcus faecalis, S. pneumoniae, and Yersinia pestis [154–156].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [154] Singh KV, Coque TM, Weinstock GM, Murray BE (1998) In vivo testing of an Enterococcus faecalis efaA mutant and use of efaA homologs for species identification. FEMS Immunol Med Microbiol 21(4):323–331 source
- Not checked yetcites [155] Berry AM, Paton JC (1996) Sequence heterogeneity of PsaA, a 37-kilodalton putative adhesin essential for virulence of Streptococcus pneumoniae. Infect Immun 64(12):5255–5262 source
- Not checked yetcites [156] Bearden SW, Perry RD (1999) The Yfe system of Yersinia pestis transports iron and manganese and is required for full virulence of plague. Mol Microbiol 32(2):403–414 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Manganese limitation therefore renders S. aureus more susceptible to oxidative stress (Fig. 2) [150].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [150] Kehl-Fie TE, Chitayat S, Hood MI, Damo S, Restrepo N, Garcia C, Munro KA, Chazin WJ, Skaar EP (2011) Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. Cell Host Microbe 10(2):158–164. doi:10.1016/j.chom.2011.07.004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“S. aureus produces two superoxide dismutases, SodA and SodM, which detoxify superoxide anion to hydrogen peroxide [148, 149].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [148] Clements MO, Watson SP, Foster SJ (1999) Characterization of the major superoxide dismutase of Staphylococcus aureus and its role in starvation survival, stress resistance, and pathogenicity. J Bacteriol 181(13):3898–3903 source
- Not checked yetcites [149] Valderas MW, Hart ME (2001) Identification and characterization of a second superoxide dismutase gene (sodM) from Staphylococcus aureus. J Bacteriol 183(11):3399–3407. doi:10.1128/JB.183.11.3399-3407.2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This suggests that the ability to regulate intracellular concentrations of manganese may also be important for bacterial pathogenesis.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In S. aureus, mutation of mntA, mntH, or mntR in the laboratory strain 8325-4 does not lead to a significant reduction in bacterial recovery in a murine skin abscess model.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
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In the paper
“Disruption of manganese acquisition reduces the virulence of a number of bacterial pathogens.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, concurrent inactivation of mntA and mntH significantly decreases bacterial recovery in this model.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Consistent with this, disruption of Nramp1 in mice leads to increased susceptibility to the intracellular pathogens Salmonella Typhimurium, Mycobacterium bovis, and Leishmania donovani [161].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [161] Vidal S, Tremblay ML, Govoni G, Gauthier S, Sebastiani G, Malo D, Skamene E, Olivier M, Jothy S, Gros P (1995) The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J Exp Med 182(3):655–666 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Disruption of mntA, mntH, mntR, or both mntA and mntH also significantly reduces intracellular survival in human endothelial cells [144].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Experiments using a fluorescent probe that is readily incorporated into the phagosome demonstrated that Nramp1 functions as a pH-dependent transporter capable of manganese efflux from the phagolysosome [158].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [158] Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, Gros P (2000) Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 192(9):1237–1248 source
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None of the sources cited for this claim have been checked yet.
In the paper
“First, the availability of manganese to intracellular pathogens is limited by the cation transporter Nramp1.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [157] Gruenheid S, Pinner E, Desjardins M, Gros P (1997) Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med 185(4):717–730 source
- Not checked yetcites [158] Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, Gros P (2000) Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 192(9):1237–1248 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Subsequent in vivo analyses revealed that calprotectin also limits bacterial growth in abscesses via chelation of manganese.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The importance of Nramp1 during human infection is suggested by studies linking certain polymorphisms in Nramp1 to an enhanced susceptibility to both M. tuberculosis and nontuberculous mycobacteria [162–164].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [162] van Crevel R, Parwati I, Sahiratmadja E, Marzuki S, Ottenhoff TH, Netea MG, van der Ven A, Nelwan RH, van der Meer JW, Alisjahbana B, van de Vosse E (2009) Infection with Mycobacterium tuberculosis Beijing genotype strains is associated with polymorphisms in SLC11A1/NRAMP1 in Indonesian patients with tuberculosis. J Infect Dis 200(11):1671–1674. doi:10.1086/648477 source
- Not checked yetcites [163] Jin J, Sun L, Jiao W, Zhao S, Li H, Guan X, Jiao A, Jiang Z, Shen A (2009) SLC11A1 (formerly NRAMP1) gene polymorphisms associated with pediatric tuberculosis in China. Clin Infect Dis 48(6):733–738. doi:10.1086/597034 source
- Not checked yetcites [164] Koh WJ, Kwon OJ, Kim EJ, Lee KS, Ki CS, Kim JW (2005) NRAMP1 gene polymorphism and susceptibility to nontuberculous mycobacterial lung diseases. Chest 128(1):94–101. doi:10.1378/chest.128.1.94 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Sequestration of manganese is an important facet of the innate immune response to bacterial infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Treatment of S. aureus with calprotectin results in enhanced susceptibility to oxidative stress through inhibition of SodA and SodM.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [150] Kehl-Fie TE, Chitayat S, Hood MI, Damo S, Restrepo N, Garcia C, Munro KA, Chazin WJ, Skaar EP (2011) Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. Cell Host Microbe 10(2):158–164. doi:10.1016/j.chom.2011.07.004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The concentration of zinc does not differ significantly between S. aureus abscesses in wild-type and calprotectin-deficient mice.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 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
“Nevertheless, the fact that S. aureus can proliferate readily in abscesses suggests the presence of systems dedicated to overcoming calprotectin-mediated manganese limitation.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Mutation of staphylococcal sodA and sodM results in decreased bacterial recovery from infected organs in a murine model of systemic infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [150] Kehl-Fie TE, Chitayat S, Hood MI, Damo S, Restrepo N, Garcia C, Munro KA, Chazin WJ, Skaar EP (2011) Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. Cell Host Microbe 10(2):158–164. doi:10.1016/j.chom.2011.07.004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“F. magna strains that express Protein L are protected from calprotectin-mediated killing [184].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [184] Akerstrom B, Bjorck L (2009) Bacterial surface protein L binds and inactivates neutrophil proteins S100A8/A9. J Immunol 183(7):4583–4592. doi:10.4049/jimmunol.0901487 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, in calprotectin-deficient mice there is no difference in bacterial recovery between wild-type and sodAsodM-inactivated S. aureus.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [150] Kehl-Fie TE, Chitayat S, Hood MI, Damo S, Restrepo N, Garcia C, Munro KA, Chazin WJ, Skaar EP (2011) Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. Cell Host Microbe 10(2):158–164. doi:10.1016/j.chom.2011.07.004 source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Conversely, human trials of zinc supplementation demonstrate protection against infectious diseases.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction
What the sources say
- Not checked yetcites [191] Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S (1995) Zinc supplementation in young children with acute diarrhea in India. N Engl J Med 333(13):839–844. doi:10.1056/NEJM199509283331304 source
- Not checked yetcites [192] Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK (1998) Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics 102(1 Pt 1):1–5 source
- Not checked yetcites [193] Lassi ZS, Haider BA, Bhutta ZA (2010) Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev (12):CD005978. doi:10.1002/14651858.CD005978.pub2 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Zinc is an essential nutrient for humans.
In the paper
“S. aureus strains possessing mutations in mntA or mntB are more sensitive to the antibacterial effects of calprotectin, further supporting the importance of manganese acquisition to staphylococcal virulence [34].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Both human and animal studies have shown a correlation between zinc deficiency and enhanced susceptibility to infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction
What the sources say
- Not checked yetcites [190] Shankar AH, Prasad AS (1998) Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 68(2 Suppl):447S–463S source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Rests on an assumption: Zinc is an essential nutrient for humans.
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
“Collectively, these results demonstrated that manganese limitation is an important innate immune response to staphylococci in tissue abscesses.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
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
“Therefore, calprotectin-mediated inhibition of bacterial superoxide defenses is an important immune response to staphylococcal abscesses.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Visceral abscesses in mice infected with S. aureus are essentially devoid of manganese and zinc.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Zur has two regulatory metal binding sites, allowing for graded expression of zinc-responsive genes in accordance with zinc availability [198].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [198] Shin JH, Jung HJ, An YJ, Cho YB, Cha SS, Roe JH (2011) Graded expression of zinc-responsive genes through two regulatory zinc-binding sites in Zur. Proc Natl Acad Sci U S A 108(12):5045–5050. doi:10.1073/pnas.1017744108 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.
- Rests on an assumption: Zinc is also an essential nutrient for bacterial pathogens.
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
“Taken together, these findings indicate a critical role for zinc in protection against infectious diseases.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Zinc is an essential nutrient for humans.
In the paper
“In elderly adults, zinc supplementation significantly reduces the incidence of infection [194].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction
What the sources say
- Not checked yetcites [194] Prasad AS, Beck FW, Bao B, Fitzgerald JT, Snell DC, Steinberg JD, Cardozo LJ (2007) Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr 85(3):837–844 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Zinc is an essential nutrient for humans.
None of the sources cited for this claim have been checked yet.
In the paper
“Resistance to both zinc and cobalt is conferred by the chromosomally encoded czrAB operon, which encodes a metal-regulated transcriptional repressor (CzrA, also known as ZntR) and a CDF antiporter (CzrB, also known as ZntA) [146, 147, 203].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [146] Kuroda M, Hayashi H, Ohta T (1999) Chromosome-determined zinc-responsible operon czr in Staphylococcus aureus strain 912. Microbiol Immunol 43(2):115–125 source
- Not checked yetcites [147] Xiong A, Jayaswal RK (1998) Molecular characterization of a chromosomal determinant conferring resistance to zinc and cobalt ions in Staphylococcus aureus. J Bacteriol 180(16):4024–4029 source
- Not checked yetcites [203] Singh VK, Xiong A, Usgaard TR, Chakrabarti S, Deora R, Misra TK, Jayaswal RK (1999) ZntR is an autoregulatory protein and negatively regulates the chromosomal zinc resistance operon znt of Staphylococcus aureus. Mol Microbiol 33(1):200–207 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The ZnuABC system is regulated by Zur, a metallo-regulatory protein of the Fur family, such that zinc import is repressed in zinc-replete conditions [196].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [196] Patzer SI, Hantke K (1998) The ZnuABC high-affinity zinc uptake system and its regulator Zur in Escherichia coli. Mol Microbiol 28(6):1199–1210 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Rests on an assumption: Zinc is also an essential nutrient for bacterial pathogens.
In the paper
“CadA is a P-type ATPase encoded by the S. aureus plasmid pI258 that mediates resistant to cadmium, lead, and zinc [204].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [204] Nucifora G, Chu L, Misra TK, Silver S (1989) Cadmium resistance from Staphylococcus aureus plasmid pI258 cadA gene results from a cadmium-efflux ATPase. Proc Natl Acad Sci U S A 86(10):3544–3548 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, there was no appreciable change in susceptibility to zinc limitation relative to wild type when mreA and mreB were inactivated [205].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [205] Lindsay JA, Foster SJ (2001) Zur: a Zn(2+)-responsive regulatory element of Staphylococcus aureus. Microbiology 147(Pt 5):1259–1266 source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Expression of copA is regulated by the copper-sensitive operon repressor (CsoR) [212, 213].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [212] Grossoehme N, Kehl-Fie TE, Ma Z, Adams KW, Cowart DM, Scott RA, Skaar EP, Giedroc DP (2011) Control of copper resistance and inorganic sulfur metabolism by paralogous regulators in Staphylococcus aureus. J Biol Chem 286(15):13522–13531. doi:10.1074/jbc.M111.220012 source
- Not checked yetcites [213] Liu T, Ramesh A, Ma Z, Ward SK, Zhang L, George GN, Talaat AM, Sacchettini JC, Giedroc DP (2007) CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator. Nat Chem Biol 3(1):60–68. doi:10.1038/nchembio844 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In S. aureus, CopA is involved in copper efflux, as evidenced by increased intracellular copper concentrations in a copA mutant [211].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [211] Sitthisak S, Knutsson L, Webb JW, Jayaswal RK (2007) Molecular characterization of the copper transport system in Staphylococcus aureus. Microbiology 153(Pt 12):4274–4283. doi:10.1099/mic.0.2007/009860-0 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Copper is an important cofactor for a number of bacterial enzymes, but like other transition metals, it is toxic if concentrations are not carefully regulated.
None of the sources cited for this claim have been checked yet.
In the paper
“Limitation of zinc availability may be beneficial to controlling S. aureus infection, as several processes that contribute to staphylococcal virulence are zinc dependent, including biofilm formation and superantigen activity [209, 210].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Dynamic changes in zinc distribution occur in response to infection and inflammation
What the sources say
- Not checked yetcites [209] Pless DD, Ruthel G, Reinke EK, Ulrich RG, Bavari S (2005) Persistence of zinc-binding bacterial superantigens at the surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activators. Infect Immun 73(9):5358–5366. doi:10.1128/IAI.73.9.5358-5366.2005 source
- Not checked yetcites [210] Conrady DG, Brescia CC, Horii K, Weiss AA, Hassett DJ, Herr AB (2008) A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms. Proc Natl Acad Sci U S A 105(49):19456–19461. doi:10.1073/pnas.0807717105 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Imaging mass spectrometry revealed that staphylococcal murine abscesses are nearly devoid of zinc.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Dynamic changes in zinc distribution occur in response to infection and inflammation
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Copper binding by CsoR results in a conformational change, causing release of operator DNA and de-repression of the copper-sensitive operon.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [212] Grossoehme N, Kehl-Fie TE, Ma Z, Adams KW, Cowart DM, Scott RA, Skaar EP, Giedroc DP (2011) Control of copper resistance and inorganic sulfur metabolism by paralogous regulators in Staphylococcus aureus. J Biol Chem 286(15):13522–13531. doi:10.1074/jbc.M111.220012 source
- Not checked yetcites [213] Liu T, Ramesh A, Ma Z, Ward SK, Zhang L, George GN, Talaat AM, Sacchettini JC, Giedroc DP (2007) CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator. Nat Chem Biol 3(1):60–68. doi:10.1038/nchembio844 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast to these functionally characterized exporters, the proteins mediating zinc uptake in S. aureus have yet to be identified.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Administration of human IL-1 to rats leads to decreased serum zinc concentrations with concomitant redistribution to various tissues such as the liver, bone marrow, and thymus [206].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Dynamic changes in zinc distribution occur in response to infection and inflammation
What the sources say
- Not checked yetcites [206] Cousins RJ, Leinart AS (1988) Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J 2(13):2884–2890 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
“Disruption of copper homeostasis reduces the virulence of select bacterial pathogens.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Deletion of copA in S. pneumoniae causes reduced virulence in a mouse pneumonia model [216].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [216] Shafeeq S, Yesilkaya H, Kloosterman TG, Narayanan G, Andrew PW, Kuipers OP, Morrissey JA (2011) The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae. Mol Microbiol. doi:10.1111/j.1365-2958.2011.07758.x source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“ATP7A is trafficked to the phagosome where it imports bactericidal levels of copper.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [220] White C, Lee J, Kambe T, Fritsche K, Petris MJ (2009) A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem 284(49):33949–33956. doi:10.1074/jbc.M109.070201 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In contrast to iron, manganese, and zinc, the levels of copper increase in response to infection and inflammation [221, 222].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [221] Arredondo M, Nunez MT (2005) Iron and copper metabolism. Mol Aspects Med 26(4–5):313–327. doi:10.1016/j.mam.2005.07.010 source
- Not checked yetcites [222] Edvinsson M, Frisk P, Molin Y, Hjelm E, Ilback NG (2008) Trace element balance is changed in infected organs during acute Chlamydophila pneumoniae infection in mice. Biometals 21(2):229–237. doi:10.1007/s10534-007-9114-7 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This effect is partially mediated by proinflammatory cytokines, which stimulate hepatic synthesis of ceruloplasmin, the major plasma copper-binding protein [223].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [223] Ramadori G, Van Damme J, Rieder H, Buschenfelde KH Meyer zum (1988) Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. Eur J Immunol 18(8):1259–1264. doi:10.1002/eji.1830180817 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, inactivation of a putative copper exporter (MctB) in M. tuberculosis significantly reduces bacterial burden in the lungs of infected guinea pigs [217].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [217] Wolschendorf F, Ackart D, Shrestha TB, Hascall-Dove L, Nolan S, Lamichhane G, Wang Y, Bossmann SH, Basaraba RJ, Niederweis M (2011) Copper resistance is essential for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 108(4):1621–1626. doi:10.1073/pnas.1009261108 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, copper-coated surfaces exhibit rapid killing of MRSA as compared with brass and stainless steel [224].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [224] Noyce JO, Michels H, Keevil CW (2006) Potential use of copper surfaces to reduce survival of epidemic meticillin-resistant Staphylococcus aureus in the healthcare environment. J Hosp Infect 63(3):289–297. doi:10.1016/j.jhin.2005.12.008 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
“Collectively, these results reveal that diverse bacterial pathogens encounter potentially toxic levels of copper in vivo, and invite the question of whether modulation of copper levels in host tissues might be an innate immune response to infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In response to interferon-gamma, macrophages increase the expression of two copper transporters, CTR1 and ATP7A.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [220] White C, Lee J, Kambe T, Fritsche K, Petris MJ (2009) A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem 284(49):33949–33956. doi:10.1074/jbc.M109.070201 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Finally, mutation of the P. aeruginosa gene cueA, an ATPase involved in protection from copper toxicity, results in a 50-fold decrease in virulence in a lethal dose murine model [218].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [218] Schwan WR, Warrener P, Keunz E, Stover CK, Folger KR (2005) Mutations in the cueA gene encoding a copper homeostasis P-type ATPase reduce the pathogenicity of Pseudomonas aeruginosa in mice. Int J Med Microbiol 295(4):237–242 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Conversely, RNAi-mediated depletion of ATP7A leads to increased bacterial survival in the phagosome [220].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [220] White C, Lee J, Kambe T, Fritsche K, Petris MJ (2009) A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem 284(49):33949–33956. doi:10.1074/jbc.M109.070201 source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For example, concomitant inactivation of both isdB and isdH leads to a significant reduction in bacterial recovery from the lungs, heart, and kidneys of mice infected intravenously with S. aureus.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Calprotectin-mediated manganese sequestration limits S. aureus growth in abscesses, in part by disrupting manganese-dependent oxidative stress defenses.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Examination of mice infected with S. aureus by IMS revealed that calprotectin co-localized to abscessed tissue in a neutrophil-dependent manner.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As discussed above, LA-ICPMS analysis of infected murine tissues allowed determination of manganese and zinc distribution in staphylococcal abscesses, and confirmed that manganese is limited in abscessed tissue.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
boosted- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: LA-ICPMS is a highly sensitive form of mass spectroscopy capable of quantifying elemental abundance within two dimensions.
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
“Emerging data suggest that host limitation of manganese is also an essential component of the immune response to staphylococcal infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
hedgeddirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Unlike iron, manganese, and zinc, host copper concentrations increase in response to infection”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite innate immune mechanisms that limit the availability of transition metals, S. aureus can proliferate in vertebrate hosts through the expression of metal acquisition systems that successfully overcome nutritional immunity.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Additional studies suggest that infection-induced redistribution of other metal ions such as copper and zinc also contribute to resistance to microbial infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The expression of high-affinity manganese transporters allows S. aureus to overcome manganese sequestration and survive within the hostile environment of an abscess.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IMS was instrumental in the identification of calprotectin as an innate immune effector responding to staphylococcal abscesses [34].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 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
“suggesting that the human immune system may exploit the toxicity of copper as an innate immune mechanism against bacterial pathogens.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
hedgedconditional- 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 preliminary studies reveal that copper-containing compounds are effectively antibacterial at concentrations that are not cytotoxic to human or animal cells.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
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
“The ability to acquire nutrients from the host, including metal ions, is critical for staphylococcal infection.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LA-ICPMS studies reveal that mature staphylococcal abscesses are essentially devoid of manganese and zinc.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, when mice were infected intranasally with S. aureus isdBH mutants, there is no significant difference in bacterial recovery from the lungs in comparison to wild type [131].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
What the sources say
- Not checked yetcites [131] Mason WJ, Skaar EP (2009) Assessing the contribution of heme-iron acquisition to Staphylococcus aureus pneumonia using computed tomography. PLoS One 4(8):e6668. doi:10.1371/journal.pone.0006668 source
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 53
- Probably not a substantial claim. 20
Every source the paper cites for this claim was checked and supports it.
In the paper
“Compared to wild-type mice, mice expressing human hemoglobin are more susceptible to S. aureus infection, as evidenced by increased colony recovery from infected organs.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Supportedcites [118] Pishchany G, McCoy AL, Torres VJ, Krause JC, Crowe JE Jr, Fabry ME, Skaar EP (2010) Specificity for human hemoglobin enhances Staphylococcus aureus infection. Cell Host Microbe 8(6):544–550. doi:10.1016/j.chom.2010.11.002 source
The Results section, “Human hemoglobin exacerbates S. aureus infection in a murine model,” reports that human-hemoglobin-expressing αHβA mice were more efficiently colonized than wild-type mice after systemic S. aureus infection. It describes enumerating bacteria from removed organs after 96 hours, supporting the claim about increased colony recovery. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
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 majority of vertebrate iron is therefore inaccessible to predominantly extracellular pathogens such as S. aureus.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: S. aureus is predominantly an extracellular pathogen.
In the paper
“In response to infection, mammalian hosts can further limit iron availability through a number of mechanisms including decreased dietary iron absorption, reduced release of iron from macrophages, and release of apolactoferrin from neutrophil granules at the site of infection [32].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host
What the sources say
- Not checked yetcites [32] Weinberg ED (2009) Iron availability and infection. Biochim Biophys Acta 1790(7):600–605. doi:10.1016/j.bbagen.2008.07.002 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
“Nutritional immunity describes the process whereby a host sequesters nutrients essential to bacterial growth, thus limiting the ability of invading pathogens to proliferate in the host environment.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Introduction
What the sources say
- Not checked yetcites [31] Kochan I (1973) The role of iron in bacterial infections, with special consideration of host-tubercle bacillus interaction. Curr Top Microbiol Immunol 60:1–30 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Staphyloferrin A is a 479 Da molecule encoded by the sfaABCD gene cluster [47, 52]. Following iron complexation by staphyloferrin A, transport across the staphylococcal membrane is mediated by the ABC transporter HtsABC, in a process powered by a separate ATPase, FhuC (Fig. 1) [47, 53].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [47] Beasley FC, Vines ED, Grigg JC, Zheng Q, Liu S, Lajoie GA, Murphy ME, Heinrichs DE (2009) Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus. Mol Microbiol 72(4):947–963. doi:10.1111/j.1365-2958.2009.06698.x source
- Not checked yetcites [52] Cotton JL, Tao J, Balibar CJ (2009) Identification and characterization of the Staphylococcus aureus gene cluster coding for staphyloferrin A. Biochemistry 48(5):1025–1035. doi:10.1021/bi801844c source
- Not checked yetcites [53] Speziali CD, Dale SE, Henderson JA, Vines ED, Heinrichs DE (2006) Requirement of Staphylococcus aureus ATP-binding cassette-ATPase FhuC for iron-restricted growth and evidence that it functions with more than one iron transporter. J Bacteriol 188(6):2048–2055. doi:10.1128/JB.188.6.2048-2055.2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In iron-replete conditions, Fur binds a consensus DNA sequence (Fur box) upstream of Fur-regulated genes, leading to transcriptional repression. In iron-deplete conditions, Fur no longer binds to Fur boxes, and transcription of Fur-regulated genes can proceed.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [51] Xiong A, Singh VK, Cabrera G, Jayaswal RK (2000) Molecular characterization of the ferric-uptake regulator, Fur, from Staphylococcus aureus. Microbiology 146(Pt 3):659–668 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Fur is an iron-dependent transcriptional regulator that is conserved among Gram-positive and Gram-negative bacteria [50].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [50] Hantke K (1981) Regulation of ferric iron transport in Escherichia coli K12: isolation of a constitutive mutant. Mol Gen Genet 182(2):288–292 source
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.
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In the paper
“Staphyloferrin B is a 448 Da compound composed of L-2,3-diaminopropionic acid, 1,2-diaminoethane, and α-ketoglutaric acid [56]. Staphyloferrin B is a product of the sbnABCDEFGHI operon, of which only SbnC, SbnE, SbnF, and SbnH are required for in vitro synthesis [57]. Transport of staphyloferrin B across the staphylococcal cell membrane is mediated by the staphylococcal iron-regulated transporter”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus produces siderophores to steal iron from transferrin
What the sources say
- Not checked yetcites [56] Drechsel H, Freund S, Nicholson G, Haag H, Jung O, Zahner H, Jung G (1993) Purification and chemical characterization of staphyloferrin B, a hydrophilic siderophore from staphylococci. Biometals 6(3):185–192 source
- Not checked yetcites [57] Cheung J, Beasley FC, Liu S, Lajoie GA, Heinrichs DE (2009) Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol Microbiol 74(3):594–608. doi:10.1111/j.1365-2958.2009.06880.x source
- Not checked yetcites [58] Dale SE, Sebulsky MT, Heinrichs DE (2004) Involvement of SirABC in iron-siderophore import in Staphylococcus aureus. J Bacteriol 186(24):8356–8362. doi:10.1128/JB.186.24.8356-8362.2004 source
- Not checked yetcites [59] Grigg JC, Cheung J, Heinrichs DE, Murphy ME (2010) Specificity of Staphyloferrin B recognition by the SirA receptor from Staphylococcus aureus. J Biol Chem 285(45):34579–34588. doi:10.1074/jbc.M110.172924 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, patients with hemochromatosis are more susceptible to infection by Yersinia enterocolitica, Vibrio vulnificans, and Listeria monocytogenes [39–42].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host
What the sources say
- Not checked yetcites [39] Vadillo M, Corbella X, Pac V, Fernandez-Viladrich P, Pujol R (1994) Multiple liver abscesses due to Yersinia enterocolitica discloses primary hemochromatosis: three cases reports and review. Clin Infect Dis 18(6):938–941 source
- Not checked yetcites [40] Barton JC, Acton RT (2009) Hemochromatosis and Vibrio vulnificus wound infections. J Clin Gastroenterol 43(9):890–893. doi:10.1097/MCG.0b013e31819069c1 source
- Not checked yetcites [41] Weinberg ED (2000) Microbial pathogens with impaired ability to acquire host iron. Biometals 13(1):85–89 source
- Not checked yetcites [42] Manso C, Rivas I, Peraire J, Vidal F, Richart C (1997) Fatal Listeria meningitis, endocarditis and pericarditis in a patient with haemochromatosis. Scand J Infect Dis 29(3):308–309 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mutation of the gene encoding FhuC, the ABC-type ATPase required for both staphyloferrin A and B uptake, results in decreased murine morbidity, but not colony recovery, in a kidney abscess model [53].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
What the sources say
- Not checked yetcites [53] Speziali CD, Dale SE, Henderson JA, Vines ED, Heinrichs DE (2006) Requirement of Staphylococcus aureus ATP-binding cassette-ATPase FhuC for iron-restricted growth and evidence that it functions with more than one iron transporter. J Bacteriol 188(6):2048–2055. doi:10.1128/JB.188.6.2048-2055.2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This result is in contrast to previously published data in which mutation of sbnE significantly decreased colony recovery in a murine kidney abscess model [74].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
What the sources say
- Not checked yetcites [74] Dale SE, Doherty-Kirby A, Lajoie G, Heinrichs DE (2004) Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Infect Immun 72(1):29–37 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
“In vertebrates, heme is the primary reservoir of iron, representing up to 80% of total body iron. This is in contrast to transferrin-bound iron, which represents less than 1% of total body iron [38].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [38] Crichton R (2001) Inorganic biochemistry of iron metabolism: from molecular mechanisms to clinical consequences, vol 2. Wiley, West Sussex 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
“Stealth side-rophores have not been described in S. aureus.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
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.
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In the paper
“Hemoglobin liberated from erythrocytes is bound by the high-affinity binding protein haptoglobin and subsequently processed by the reticuloendothelial system [88]. Additionally, free heme released into plasma can be sequestered by albumin, hemopexin, and alpha-1-microglobulin [86, 88, 89].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [86] Young NS, Gerson SL, High KA (2006) Clinical hematology, vol 1. Mosby Elsevier, Philadelphia
- Not checked yetcites [88] Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409(6817):198–201. doi:10.1038/35051594 source
- Not checked yetcites [89] Allhorn M, Berggard T, Nordberg J, Olsson ML, Akerstrom B (2002) Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties. Blood 99(6):1894–1901 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Inactivation of either the catecholamine transporter (Sst) alone, both siderophore operons (sfa and sbn), or both siderophore transporters (Hts and Sir) yields a reduction in colony recovery from the hearts of systemically infected mice.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
What the sources say
- Not checked yetcites [60] Beasley FC, Marolda CL, Cheung J, Buac S, Heinrichs DE (2011) Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by staphyloferrin a, staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79(6):2345–2355. doi:10.1128/IAI.00117-11 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, combined inactivation of sfa, sbn, and sst results in reduced colony recovery from the heart and liver, whereas combined inactivation of sst, sirA, and hts decreases colony recovery in heart, liver, and kidney.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Iron acquisition by siderophores contributes to staphylococcal virulence
What the sources say
- Not checked yetcites [60] Beasley FC, Marolda CL, Cheung J, Buac S, Heinrichs DE (2011) Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by staphyloferrin a, staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79(6):2345–2355. doi:10.1128/IAI.00117-11 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
“Although siderophore-mediated iron acquisition promotes staphylococcal growth in iron-limited conditions in vitro and in vivo, the preferred iron source for S. aureus is heme.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Unlike human heme-oxygenases which degrade heme to iron and the chromophore biliverdin, IsdG and IsdI degrade heme to iron and a novel chromophore, staphylobilin [104].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [104] Reniere ML, Ukpabi GN, Harry SR, Stec DF, Krull R, Wright DW, Bachmann BO, Murphy ME, Skaar EP (2010) The IsdG-family of haem oxygenases degrades haem to a novel chromophore. Mol Microbiol 75(6):1529–1538. doi:10.1111/j.1365-2958.2010.07076.x 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
“Interestingly, mutation of isdDEF decreases, but does not abolish, the ability of S. aureus to grow on heme, suggesting that there are IsdDEF-independent mechanisms of heme import [101].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [101] Mazmanian SK, Skaar EP, Gaspar AH, Humayun M, Gornicki P, Jelenska J, Joachmiak A, Missiakas DM, Schneewind O (2003) Passage of heme-iron across the envelope of Staphylococcus aureus. Science 299(5608):906–909. doi:10.1126/science.1081147 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Deletion of either isdG or isdI results in a decreased ability to utilize heme, indicating that these enzymes are not functionally redundant [105].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [105] Reniere ML, Skaar EP (2008) Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem. Mol Microbiol 69(5):1304–1315. doi:10.1111/j.1365-2958.2008.06363.x source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Both isdG and isdI are transcriptionally regulated by iron, such that maximal expression occurs in iron-limited conditions. IsdG is also post-transcriptionally regulated by heme, as protein stability is enhanced in the presence of heme [105].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [105] Reniere ML, Skaar EP (2008) Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem. Mol Microbiol 69(5):1304–1315. doi:10.1111/j.1365-2958.2008.06363.x 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 mechanisms protect the host from heme toxicity, while also limiting the availability of heme and hemoproteins to invading pathogens.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The two-component system upstream of hrtAB, subsequently named the heme sensor system (HssR and HssS), is required for the adaptive response to heme toxicity and activates transcription of hrtAB [106].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
What the sources say
- Not checked yetcites [106] Torres VJ, Stauff DL, Pishchany G, Bezbradica JS, Gordy LE, Iturregui J, Anderson KL, Dunman PM, Joyce S, Skaar EP (2007) A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe 1(2):109–119. doi:10.1016/j.chom.2007.03.001 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, passive immunization with anti-Hla antibodies or active immunization with nontoxigenic Hla is protective in animal models of staphylococcal infection [108, 115].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [108] Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, DeLeo FR (2010) Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 202(7):1050–1058. doi:10.1086/656043 source
- Not checked yetcites [115] Ragle BE, Bubeck Wardenburg J (2009) Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect Immun 77(7):2712–2718. doi:10.1128/IAI.00115-09 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, S. aureus senses heme through HssRS, increasing transcription of hrtAB, which leads to alleviation of heme toxicity.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > S. aureus preferentially acquires iron from heme and hemoproteins
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IsdA and IsdB were identified as vaccine candidates using “reverse vaccinology” [119], and subsequent studies confirmed that immunization with these proteins is protective in murine models of infection [117, 120–123].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [119] Maione D, Margarit I, Rinaudo CD, Masignani V, Mora M, Scarselli M, Tettelin H, Brettoni C, Iacobini ET, Rosini R, D’Agostino N, Miorin L, Buccato S, Mariani M, Galli G, Nogarotto R, Nardi Dei V, Vegni F, Fraser C, Mancuso G, Teti G, Madoff LC, Paoletti LC, Rappuoli R, Kasper DL, Telford JL, Grandi G (2005) Identification of a universal group B streptococcus vaccine by multiple genome screen. Science 309(5731):148–150. doi:10.1126/science.1109869 source
- Not checked yetcites [117] Kim HK, DeDent A, Cheng AG, McAdow M, Bagnoli F, Missiakas DM, Schneewind O (2010) IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge. Vaccine 28(38):6382–6392. doi:10.1016/j.vaccine.2010.02.097 source
- Not checked yetcites [120] Stranger-Jones YK, Bae T, Schneewind O (2006) Vaccine assembly from surface proteins of Staphylococcus aureus. Proc Natl Acad Sci U S A 103(45):16942–16947. doi:10.1073/pnas.0606863103 source
- Not checked yetcites [121] Kuklin NA, Clark DJ, Secore S, Cook J, Cope LD, McNeely T, Noble L, Brown MJ, Zorman JK, Wang XM, Pancari G, Fan H, Isett K, Burgess B, Bryan J, Brownlow M, George H, Meinz M, Liddell ME, Kelly R, Schultz L, Montgomery D, Onishi J, Losada M, Martin M, Ebert T, Tan CY, Schofield TL, Nagy E, Meineke A, Joyce JG, Kurtz MB, Caulfield MJ, Jansen KU, McClements W, Anderson AS (2006) 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(4):2215–2223. doi: source
- Not checked yetcites [122] Clarke SR, Brummell KJ, Horsburgh MJ, McDowell PW, Mohamad SA, Stapleton MR, Acevedo J, Read RC, Day NP, Peacock SJ, Mond JJ, Kokai-Kun JF, Foster SJ (2006) Identification of in vivo-expressed antigens of Staphylococcus aureus and their use in vaccinations for protection against nasal carriage. J Infect Dis 193(8):1098–1108. doi:10.1086/501471 source
- Not checked yetcites [123] Ebert T, Smith S, Pancari G, Clark D, Hampton R, Secore S, Towne V, Fan H, Wang XM, Wu X, Ernst R, Harvey BR, Finnefrock AC, Wang F, Tan C, Durr E, Cope L, Anderson A, An Z, McNeely T (2010) 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(4):113–128. doi:10.3233/HAB-2010-0235 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“IsdA binds both fibrinogen and fibronectin in vitro, indicating a potential role as an iron-regulated adhesin [125].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [125] Clarke SR, Wiltshire MD, Foster SJ (2004) IsdA of Staphylococcus aureus is a broad spectrum, iron-regulated adhesin. Mol Microbiol 51(5):1509–1519. doi:10.1111/j.1365-2958.2003.03938.x source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Consistent with this hypothesis, IsdA facilitates binding to human desquamated epithelial cells, and promotes nasal colonization in rats [122, 126, 127].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [122] Clarke SR, Brummell KJ, Horsburgh MJ, McDowell PW, Mohamad SA, Stapleton MR, Acevedo J, Read RC, Day NP, Peacock SJ, Mond JJ, Kokai-Kun JF, Foster SJ (2006) Identification of in vivo-expressed antigens of Staphylococcus aureus and their use in vaccinations for protection against nasal carriage. J Infect Dis 193(8):1098–1108. doi:10.1086/501471 source
- Not checked yetcites [126] Corrigan RM, Miajlovic H, Foster TJ (2009) Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells. BMC Microbiol 9:22. doi:10.1186/1471-2180-9-22 source
- Not checked yetcites [127] Clarke SR, Andre G, Walsh EJ, Dufrene YF, Foster TJ, Foster SJ (2009) Iron-regulated surface determinant protein A mediates adhesion of Staphylococcus aureus to human corneocyte envelope proteins. Infect Immun 77(6):2408–2416. doi:10.1128/IAI.01304-08 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mutation of isdA also leads to increased susceptibility to hydrogen peroxide and to killing by human neutrophils [129].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [129] Palazzolo-Ballance AM, Reniere ML, Braughton KR, Sturdevant DE, Otto M, Kreiswirth BN, Skaar EP, DeLeo FR (2008) Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J Immunol 180(1):500–509 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“By decreasing staphylococcal cell hydrophobicity, IsdA increases the resistance of S. aureus to antimicrobial compounds produced by human sebum, as well as other antimicrobial peptides [128].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [128] Clarke SR, Mohamed R, Bian L, Routh AF, Kokai-Kun JF, Mond JJ, Tarkowski A, Foster SJ (2007) The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host Microbe 1(3):199–212. doi:10.1016/j.chom.2007.04.005 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
“In addition to its role as a heme-binding protein, there is evidence that IsdA also contributes to staphylococcal pathogenesis through roles in both adhesion to host tissues and resistance to innate immune responses.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Bacteria, like humans, must acquire manganese and regulate its intracellular concentration.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection
What the sources say
- Not checked yetcites [136] Jakubovics NS, Jenkinson HF (2001) Out of the iron age: new insights into the critical role of manganese homeostasis in bacteria. Microbiology 147(Pt 7):1709–1718 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.
- Rests on an assumption: Manganese is an essential nutrient for both eukaryotic and prokaryotic organisms.
In the paper
“Upon entering the cytoplasm, heme is degraded by IsdG or IsdI to liberate iron, a process that also contributes to staphylococcal virulence.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [105] Reniere ML, Skaar EP (2008) Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem. Mol Microbiol 69(5):1304–1315. doi:10.1111/j.1365-2958.2008.06363.x source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Inactivation of either htsB or htsC significantly reduces heme acquisition and decreases bacterial recovery and abscess formation in mice infected systemically with S. aureus [54].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > S. aureus overcomes nutritional immunity to obtain iron from the host > Heme acquisition is essential to the virulence of S. aureus
What the sources say
- Not checked yetcites [54] Skaar EP, Humayun M, Bae T, DeBord KL, Schneewind O (2004) Iron-source preference of Staphylococcus aureus infections. Science 305(5690):1626–1628. doi:10.1126/science.1099930 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mutation of mntA in S. aureus results in a reduced growth rate in metal-depleted minimal media, a phenotype that is reversible upon addition of manganese.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 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 S. aureus genome encodes MntABC-type (mntABC) and Nramp-type (mntH) manganese transporters, both of which have been functionally characterized.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 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.
In the paper
“Inactivation of the manganese efflux protein MntE in S. pneumoniae reduces nasal colonization and bloodstream invasion in mice, despite an increased resistance to reactive oxygen species [142].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [142] Rosch JW, Gao G, Ridout G, Wang YD, Tuomanen EI (2009) Role of the manganese efflux system mntE for signalling and pathogenesis in Streptococcus pneumoniae. Mol Microbiol 72(1):12–25. doi:10.1111/j.1365-2958.2009.06638.x 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 Nramp-type manganese transporter MntH is a critical virulence determinant for Brucella abortus [151].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [151] Anderson ES, Paulley JT, Gaines JM, Valderas MW, Martin DW, Menscher E, Brown TD, Burns CS, Roop RM 2nd (2009) The manganese transporter MntH is a critical virulence determinant for Brucella abortus 2308 in experimentally infected mice. Infect Immun 77(8):3466–3474. doi:10.1128/IAI.00444-09 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Additionally, S. aureus employs superoxide dismutase-independent mechanisms to detoxify superoxide, a process that is also dependent on manganese [144].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Bacterial acquisition of manganese is facilitated by high-affinity transporters
What the sources say
- Not checked yetcites [144] Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286 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
“Similarly, acquisition of manganese is required for intracellular survival and virulence of Salmonella enterica [152].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [152] Boyer E, Bergevin I, Malo D, Gros P, Cellier MF (2002) Acquisition of Mn(II) in addition to Fe(II) is required for full virulence of Salmonella enterica serovar Typhimurium. Infect Immun 70(11):6032–6042 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
“Disruption of MntABC in Neisseria gonorrhoeae reduces intracellular survival and biofilm formation [153].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Manganese acquisition contributes to the virulence of bacterial pathogens
What the sources say
- Not checked yetcites [153] Lim KH, Jones CE, vanden Hoven RN, Edwards JL, Falsetta ML, Apicella MA, Jennings MP, McEwan AG (2008) Metal binding specificity of the MntABC permease of Neisseria gonorrhoeae and its influence on bacterial growth and interaction with cervical epithelial cells. Infect Immun 76(8):3569–3576. doi:10.1128/IAI.01725-07 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
“Nramp1 is an integral membrane protein expressed by professional phagocytes.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [157] Gruenheid S, Pinner E, Desjardins M, Gros P (1997) Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med 185(4):717–730 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
“Upon phagocytosis, Nramp1 is recruited to the phagosome, where it remains during the maturation of phagosomes into phagolysosomes [157].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [157] Gruenheid S, Pinner E, Desjardins M, Gros P (1997) Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med 185(4):717–730 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
“Additional studies suggest that Nramp1 may also transport other cations such as iron and zinc [159, 160], and therefore may participate in limitation of multiple metals to intracellular pathogens.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [159] Forbes JR, Gros P (2003) Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood 102(5):1884–1892. doi:10.1182/blood-2003-02-0425 source
- Not checked yetcites [160] Goswami T, Bhattacharjee A, Babal P, Searle S, Moore E, Li M, Blackwell JM (2001) Natural-resistance-associated macrophage protein 1 is an H+/bivalent cation antiporter. Biochem J 354(Pt 3):511–519 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
“In contrast, abscesses in mice lacking calprotectin contain manganese levels equivalent to those of surrounding tissue, as well as significantly increased bacterial burdens compared with wild-type mice.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 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
“This renders calprotectin-treated S. aureus more susceptible to killing by neutrophils, which exert antimicrobial activity partly through the generation of reactive oxygen species (Fig. 2).”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The role of manganese in staphylococcal infection > Vertebrate hosts sequester manganese as an innate immune response to bacterial infection
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
“In children, zinc supplementation reduces the duration and severity of acute diarrhea, and reduces the incidence of lower respiratory tract infection [191–193].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction
What the sources say
- Not checked yetcites [191] Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S (1995) Zinc supplementation in young children with acute diarrhea in India. N Engl J Med 333(13):839–844. doi:10.1056/NEJM199509283331304 source
- Not checked yetcites [192] Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK (1998) Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics 102(1 Pt 1):1–5 source
- Not checked yetcites [193] Lassi ZS, Haider BA, Bhutta ZA (2010) Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev (12):CD005978. doi:10.1002/14651858.CD005978.pub2 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.
- Rests on an assumption: Zinc is an essential nutrient for humans.
None of the sources cited for this claim have been checked yet.
In the paper
“Czc-type exporters have subsequently been postulated to mediate efflux of zinc in other bacteria, including P. aeruginosa and S. aureus [146, 202].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [146] Kuroda M, Hayashi H, Ohta T (1999) Chromosome-determined zinc-responsible operon czr in Staphylococcus aureus strain 912. Microbiol Immunol 43(2):115–125 source
- Not checked yetcites [202] Hassan MT, van der Lelie D, Springael D, Romling U, Ahmed N, Mergeay M (1999) Identification of a gene cluster, czr, involved in cadmium and zinc resistance in Pseudomonas aeruginosa. Gene 238(2):417–425 source
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: 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
“A low-affinity zinc transporter, ZupT, was identified in E. coli based on similarity to eukaryotic zinc transporters of the ZIP family [199].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [199] Grass G, Wong MD, Rosen BP, Smith RL, Rensing C (2002) ZupT is a Zn(II) uptake system in Escherichia coli. J Bacteriol 184(3):864–866 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.
- Rests on an assumption: Zinc is also an essential nutrient for bacterial pathogens.
In the paper
“ZnuABC is a high-affinity ABC-type zinc transporter best characterized in E. coli, consisting of a periplasmic binding protein (ZnuA), membrane permease (ZnuB), and ATPase (ZnuC) [196].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [196] Patzer SI, Hantke K (1998) The ZnuABC high-affinity zinc uptake system and its regulator Zur in Escherichia coli. Mol Microbiol 28(6):1199–1210 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.
- Rests on an assumption: Zinc is also an essential nutrient for bacterial pathogens.
In the paper
“Another zinc exporter (CzcCBA) was identified in Ralstonia metallidurans, and also mediates efflux of cobalt and cadmium [201].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [201] Nies DH, Silver S (1989) Plasmid-determined inducible efflux is responsible for resistance to cadmium, zinc, and cobalt in Alcaligenes eutrophus. J Bacteriol 171(2):896–900 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
“Zinc export is essential for maintenance of homeostasis, and is achieved primarily through P-type ATPases which couple ATP hydrolysis to transport of zinc and other metals across the cell membrane.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [200] Rensing C, Mitra B, Rosen BP (1997) The zntA gene of Escherichia coli encodes a Zn(II)-translocating P-type ATPase. Proc Natl Acad Sci U S A 94(26):14326–14331 source
- Not checked yetcites [201] Nies DH, Silver S (1989) Plasmid-determined inducible efflux is responsible for resistance to cadmium, zinc, and cobalt in Alcaligenes eutrophus. J Bacteriol 171(2):896–900 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.
- Rests on an assumption: Zinc concentrations must be carefully regulated, as excess zinc can inappropriately bind to thiol groups of bacterial proteins and interfere with their function.
- Rests on an assumption: In bacteria, zinc homeostasis is achieved through coordinated regulation of import and export.
In the paper
“Zinc-binding proteins, which constitute an average of 5% of bacterial proteomes [195], participate in diverse processes such as regulation of virulence factors, metabolism, and inactivation of antibiotics.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [195] Andreini C, Banci L, Bertini I, Rosato A (2006) Zinc through the three domains of life. J Proteome Res 5(11):3173–3178. doi:10.1021/pr0603699 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.
- Rests on an assumption: Zinc is also an essential nutrient for bacterial pathogens.
In the paper
“ZntA in E. coli mediates efflux of both zinc and cadmium [200].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Bacterial mechanisms of zinc homeostasis
What the sources say
- Not checked yetcites [200] Rensing C, Mitra B, Rosen BP (1997) The zntA gene of Escherichia coli encodes a Zn(II)-translocating P-type ATPase. Proc Natl Acad Sci U S A 94(26):14326–14331 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
“Similarly, IL-6 administration to mice leads to hypozince-mia and increased hepatic zinc concentration through upregulation of the zinc transporter Zip14 in hepatocytes [207, 208].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Dynamic changes in zinc distribution occur in response to infection and inflammation
What the sources say
- Not checked yetcites [207] Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340(6):448–454. doi:10.1056/NEJM199902113400607 source
- Not checked yetcites [208] Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A 102(19):6843–6848. doi:10.1073/pnas.0502257102 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
“However, zinc levels within the staphylococcal abscess are unaffected by genetic defects in calprotectin production, raising the possibility that additional host factors contribute to zinc limitation in abscesses [34].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > The contribution of zinc to the host-pathogen interaction > Dynamic changes in zinc distribution occur in response to infection and inflammation
What the sources say
- Not checked yetcites [34] Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965. doi:10.1126/science.1152449 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In B. subtilis and L. monocytogenes, CopZ interacts and exchanges copper with CopA, and is therefore predicted to protect bacteria from the inappropriate binding of copper to cytoplasmic proteins [214, 215].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [214] Banci L, Bertini I, Ciofi-Baffoni S, Del Conte R, Gonnelli L (2003) Understanding copper trafficking in bacteria: interaction between the copper transport protein CopZ and the N-terminal domain of the copper ATPase CopA from Bacillus subtilis. Biochemistry 42(7):1939–1949. doi:10.1021/bi027096p source
- Not checked yetcites [215] Radford DS, Kihlken MA, Borrelly GP, Harwood CR, Le Brun NE, Cavet JS (2003) CopZ from Bacillus subtilis interacts in vivo with a copper exporting CPx-type ATPase CopA. FEMS Microbiol Lett 220(1):105–112 source
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: 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
“Copper-containing biocides have shown promise as hand sanitization gels and environmental disinfectants [226, 227].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [226] Hall TJ, Wren MW, Jeanes A, Gant VA (2009) A comparison of the antibacterial efficacy and cytotoxicity to cultured human skin cells of 7 commercial hand rubs and Xgel, a new copper-based biocidal hand rub. Am J Infect Control 37(4):322–326. doi:10.1016/j.ajic.2008.09.011 source
- Not checked yetcites [227] Gant VA, Wren MW, Rollins MS, Jeanes A, Hickok SS, Hall TJ (2007) Three novel highly charged copper-based biocides: safety and efficacy against healthcare-associated organisms. J Antimicrob Chemother 60(2):294–299. doi:10.1093/jac/dkm201 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
“The importance of copper to the vertebrate immune response is demonstrated by copper-deficient mice, which exhibit an impaired humoral immune response and enhanced susceptibility to a variety of bacterial pathogens [219, 220].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [219] Prohaska JR, Lukasewycz OA (1981) Copper deficiency suppresses the immune response of mice. Science 213(4507):559–561 source
- Not checked yetcites [220] White C, Lee J, Kambe T, Fritsche K, Petris MJ (2009) A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem 284(49):33949–33956. doi:10.1074/jbc.M109.070201 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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, in addition to nutritional immunity mediated by metal ion sequestration, vertebrate hosts can increase metal ion concentration in certain environments to kill bacterial pathogens.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
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
“IMS can be used to image single microbial colonies, bacteria growing in biofilms, interactions between two different microbes, and poly-microbial communities [231].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
What the sources say
- Not checked yetcites [231] Watrous JD, Dorrestein PC (2011) Imaging mass spectrometry in microbiology. Nat Rev Microbiol 9(9):683–694. doi:10.1038/nrmicro2634 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.
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
“LA-ICPMS therefore allows for determination of both spatial distribution of metal ions as well as their absolute concentrations in a range of infected tissues.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
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.
- Rests on an assumption: LA-ICPMS is a highly sensitive form of mass spectroscopy capable of quantifying elemental abundance within two dimensions.
In the paper
“IMS has been used to analyze proteins, peptides, lipids, drugs, and metabolites [229].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
What the sources say
- Not checked yetcites [229] Seeley EH, Caprioli RM (2011) MALDI imaging mass spectrometry of human tissue: method challenges and clinical perspectives. Trends Biotechnol 29(3):136–143. doi:10.1016/j.tibtech.2010.12.002 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.
- Rests on an assumption: Whereas sample preparation for conventional proteomic analyses results in disruption of tissue architecture, IMS allows for demonstration of sample distribution in intact tissues.
In the paper
“Furthermore, IMS can be combined with additional imaging modalities such as magnetic resonance imaging to provide a three-dimensional co-registration of proteomic data with anatomy [230].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
What the sources say
- Not checked yetcites [230] Sinha TK, Khatib-Shahidi S, Yankeelov TE, Mapara K, Ehtesham M, Cornett DS, Dawant BM, Caprioli RM, Gore JC (2008) Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging. Nat Methods 5(1):57–59. doi:10.1038/nmeth1147 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.
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 ability to characterize microbial physiology in vivo, together with the capability to assess host immune responses, provides an opportunity for comprehensive study of bacterial infections.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“S. aureus strains inactivated for the hydrogen peroxide-reducing enzymes KatA and AhpC are more sensitive to copper toxicity, further supporting oxidative stress as a mechanism for copper-mediated staphylococcal killing.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [228] Baker J, Sitthisak S, Sengupta M, Johnson M, Jayaswal RK, Morrissey JA (2010) Copper stress induces a global stress response in Staphylococcus aureus and represses sae and agr expression and biofilm formation. Appl Environ Microbiol 76(1):150–160. doi:10.1128/AEM.02268-09 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.
- Rests on an assumption: Like iron, copper can interact with hydrogen peroxide to generate damaging reactive oxygen species.
In the paper
“IMS uses matrix-assisted laser desorption/ionization time of flight to directly analyze a variety of molecules in tissue sections.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Imaging mass spectrometry, a powerful tool for the study of metal ion distribution during bacterial infection
What the sources say
- Not checked yetcites [229] Seeley EH, Caprioli RM (2011) MALDI imaging mass spectrometry of human tissue: method challenges and clinical perspectives. Trends Biotechnol 29(3):136–143. doi:10.1016/j.tibtech.2010.12.002 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.
- Rests on an assumption: Whereas sample preparation for conventional proteomic analyses results in disruption of tissue architecture, IMS allows for demonstration of sample distribution in intact tissues.
In the paper
“In response to copper exposure, S. aureus initiates a transcriptional program characterized by induction of oxidative stress and misfolded protein responses, suggesting that copper toxicity results in increased oxidative stress and protein damage [228].”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Exploiting transition metals to battle bacterial pathogens: the example of copper
What the sources say
- Not checked yetcites [228] Baker J, Sitthisak S, Sengupta M, Johnson M, Jayaswal RK, Morrissey JA (2010) Copper stress induces a global stress response in Staphylococcus aureus and represses sae and agr expression and biofilm formation. Appl Environ Microbiol 76(1):150–160. doi:10.1128/AEM.02268-09 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.
- Rests on an assumption: Like iron, copper can interact with hydrogen peroxide to generate damaging reactive oxygen species.
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
“Iron acquisition is critical to S. aureus virulence, and therefore is an attractive target for the development of new antimicrobials and vaccines.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
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
“The success of S. aureus as a human pathogen is facilitated by its ability to infect and survive within diverse host tissues.”
§ Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity > Concluding remarks
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: 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 relies on this without support.
Iron is necessary for bacterial proliferation.
“Since iron is necessary for bacterial proliferation, S. aureus must circumvent iron sequestration in order to successfully infect host tissues.”
The paper relies on this without support.
Extracellular iron released in vertebrates is tightly bound by transferrin and lactoferrin.
“Furthermore, any iron released into the extracellular environment is tightly bound to the high-affinity iron-scavenging glycoproteins transferrin and lactoferrin.”
The paper relies on this without support.
S. aureus is predominantly an extracellular pathogen.
“The majority of vertebrate iron is therefore inaccessible to predominantly extracellular pathogens such as S. aureus.”
The paper relies on this without support.
Manganese is an essential nutrient for both eukaryotic and prokaryotic organisms.
“Manganese is an essential nutrient for both eukaryotic and prokaryotic organisms.”
The paper relies on this without support.
Zinc is an essential nutrient for humans.
“Zinc is an essential nutrient for humans.”
The paper relies on this without support.
Zinc is also an essential nutrient for bacterial pathogens.
“Zinc is also an essential nutrient for bacterial pathogens.”
The paper relies on this without support.
Zinc concentrations must be carefully regulated, as excess zinc can inappropriately bind to thiol groups of bacterial proteins and interfere with their function.
“Zinc concentrations must be carefully regulated, as excess zinc can inappropriately bind to thiol groups of bacterial proteins and interfere with their function.”
The paper relies on this without support.
In bacteria, zinc homeostasis is achieved through coordinated regulation of import and export.
“In bacteria, zinc homeostasis is achieved through coordinated regulation of import and export.”
The paper relies on this without support.
Bacteria express both high- and low-affinity zinc importers.
“Bacteria express both high- and low-affinity zinc importers.”
The paper relies on this without support.
Copper is an important cofactor for a number of bacterial enzymes, but like other transition metals, it is toxic if concentrations are not carefully regulated.
“Copper is an important cofactor for a number of bacterial enzymes, but like other transition metals, it is toxic if concentrations are not carefully regulated.”
The paper relies on this without support.
Like iron, copper can interact with hydrogen peroxide to generate damaging reactive oxygen species.
“Like iron, copper can interact with hydrogen peroxide to generate damaging reactive oxygen species.”
The paper relies on this without support.
Whereas sample preparation for conventional proteomic analyses results in disruption of tissue architecture, IMS allows for demonstration of sample distribution in intact tissues.
“Whereas sample preparation for conventional proteomic analyses results in disruption of tissue architecture, IMS allows for demonstration of sample distribution in intact tissues.”
The paper relies on this without support.
LA-ICPMS is a highly sensitive form of mass spectroscopy capable of quantifying elemental abundance within two dimensions.
“LA-ICPMS is a highly sensitive form of mass spectroscopy capable of quantifying elemental abundance within two dimensions.”
The paper relies on this without support.
Infection of tissues such as bone, lung, or heart may not involve defined abscesses.
“infection of other tissues such as bone, lung, or heart may not be accompanied by formation of defined abscesses”
The paper relies on this without support.
Essential metal nutrient availability may differ among host tissues.
“the availability of essential metal nutrients may differ among host tissues”
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
“Acquisition of heme by the Isd system is critical for S. aureus pathogenesis (Cassat and Skaar, 2012).”
From Iron in infection and immunity (2013) · cites this paper as Cassat and Skaar, 2012
In the citing paper
“The production of siderophores contributes to the virulence of a variety of pathogens, including S. aureus, Escherichia coli, Legionella pneumophila, and Bacillus anthracis, among others (Cassat and Skaar, 2012).”
From Iron in infection and immunity (2013) · cites this paper as Cassat and Skaar, 2012
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
RetractedNeutrophil Extracellular Traps Kill Bacteria
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004) · Science · doi:10.1126/science.1092385 · Cited by 10,268
Acute-Phase Proteins and Other Systemic Responses to Inflammation
Gabay, C., & Kushner, I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400607 · Cited by 6,734
Journal of Biological Chemistry
Kurkinensp, M., CondongT, M. R., Blumberg, B., Barlow, D. P., Quiñones, S., Sausg, J., & Pihlajaniemisyy, T. (2021) · Journal of Biological Chemistry · doi:10.1074/jbc · Cited by 3,427
Methicillin-Resistant S. aureus Infections among Patients in the Emergency Department
Moran, G. J., Krishnadasan, A., Gorwitz, R. J., Fosheim, G. E., McDougal, L. K., Carey, R. B., & Talan, D. A. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055356 · Cited by 2,285
Lew, D. P., & Waldvogel, F. A. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16727-5 · Cited by 1,988
David, M. Z., & Daum, R. S. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00081-09 · Cited by 1,972
Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron
Flo, T. H., Smith, K. D., Sato, S., Rodriguez, D. J., Holmes, M. A., Strong, R. K., Akira, S., & Aderem, A. (2004) · Nature · doi:10.1038/nature03104 · Cited by 1,877
Urban, C. F., Ermert, D., Schmid, M., Abed, U. A., Goosmann, C., Nacken, W. K. F., Brinkmann, V., Jungblut, P. R., & Zychlinsky, A. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000639 · Cited by 1,720
Identification of the haemoglobin scavenger receptor
Kristiansen, M., Graversen, J. H., Jacobsen, C., Sonne, O., Hoffman, H.-J., Law, S. K. A., & Moestrup, S. K. (2001) · Nature · doi:10.1038/35051594 · Cited by 1,712
Research works printed but not linked: 1
- Young NS, Gerson SL, High KA (2006) Clinical hematology, vol 1. Mosby Elsevier, Philadelphia
Cited by
Sorted by citations
Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus
Foster, T. J., Geoghegan, J. A., Ganesh, V. K., & Höök, M. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro3161 · Cited by 1,606
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-citationIron 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-citationChen, B., Yu, P., Chan, W. N., Xie, F., Zhang, Y., Liang, L., Leung, K. T., Lo, K. W., Yu, J., Tse, G. M. K., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01679-y · Cited by 420
The Role of Macrophages in Staphylococcus aureus Infection
Pidwill, G. R., Gibson, J. F., Cole, J., Renshaw, S. A., & Foster, S. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.620339 · Cited by 360
Metadata
- Authors
- Cassat, J. E., & Skaar, E. P.
- Affiliations
- Vanderbilt University Medical Center (US)
- Corresponding author
- Skaar, Eric P.
- Venue
- Seminars in Immunopathology
- Published
- 2011-11-03
- Volume
- 34
- Issue
- 2
- Pages
- 215-235
- ISSN
- 1863-2297 (ISSN-L)
- 1863-2300
- PMC
- PMC3796439
- OpenAlex
- W1976196422
- Cited by
- 155
- References
- 232
- Citations by year
- 2026: 16 · 2025: 8 · 2024: 18 · 2023: 7 · 2022: 6 · 2021: 12 · 2020: 18 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 7 · 2015: 8 · 2014: 8 · 2013: 11 · 2012: 7
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Seminars in Immunopathology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Burroughs Wellcome Fund
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI073843, AI091771, L40 AI096516, AI0169233, R01AI069233, R56AI091771, U54AI057157, R01AI073843, R01AI101171, R21AI107233)
- National Center for Research Resources (S10RR026742)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD060554)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Staphylococcus aureus, nutritional immunity, transition metals, bacterial virulence, antioxidant defense, host-pathogen interaction
- MeSH terms
- Animals, Copper, Humans, Ions, Manganese, Metals, Mass Spectrometry, Staphylococcal Infections, Staphylococcus aureus, Zinc, 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 2026-10-05, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-05 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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