Specificity for human hemoglobin enhances Staphylococcus aureus infection
Open accessAbstract
SUMMARY Iron is required for bacterial proliferation and Staphylococcus aureus steals this metal from host hemoglobin during invasive infections. This process involves hemoglobin binding to the cell wall of S. aureus, heme extraction, passage through the cell envelope, and degradation to release free iron. Herein we demonstrate an enhanced ability of S. aureus to bind hemoglobin derived from humans as compared to other mammals. Increased specificity for human hemoglobin (hHb) translates into an improved ability to acquire iron and is entirely dependent on the staphylococcal hemoglobin receptor IsdB. This feature affects host-pathogen interaction as demonstrated by the increased susceptibility of hHb expressing mice to systemic staphylococcal infection. Interestingly, enhanced utilization of human hemoglobin is not a uniform property of all bacterial pathogens. These results suggest a step in the evolution of S. aureus to better colonize the human host and establish hHb expressing mice as a model of S. aureus pathogenesis.
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Claims the paper makes
11 of 24 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Capture of hemoglobin by the receptor IsdB is a critical step in heme-iron acquisition.
“A critical step in heme-iron acquisition is the capture of hemoglobin by the hemoglobin receptor IsdB (Mazmanian et al., 2003; Pishchany et al., 2009; Torres et al., 2006).”
Quote in the paperSubstantial claim2 of 3 sources checked - Premisecitation
The ΔisdB mutant grows normally when iron is supplied from sources other than hemoglobin.
“Notably, ΔisdB does not display an altered growth pattern when non-hemoglobin sources of iron are available (Torres et al., 2006).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Torres et al., 2006 source
The Results (Fig. 5B; page unavailable) report that inactivating isdB did not impair growth when hemin was the sole iron source. This supports the claim for hemin, but the paper does not establish normal ΔisdB growth with non-hemoglobin iron sources generally. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Premisecitation
When iron is scarce, as during infection, hemoglobin is a favored iron source that can supply enough iron for S. aureus growth.
“In iron-limiting conditions such as those encountered during infection (Pishchany et al., 2009; Reniere and Skaar, 2008), hemoglobin is a preferred source of iron that is sufficient to provide S. aureus with iron necessary for growth (Skaar et al., 2004; Torres et al., 2006).”
Quote in the paperSubstantial claim1 of 3 sources checked - Findingcitation
S. aureus IsdB binds human hemoglobin with a much stronger KD (5.5 × 10−8 M) than B. anthracis IsdX1 (7.3 × 10−6 M).
“S. aureus IsdB binds hHb with a much stronger KD value (5.5 × 10−8 M) than the B. anthracis hemoglobin binding protein IsdX1 (7.3 × 10−6 M) (Maresso et al., 2008).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Maresso et al., 2008 source
The section “IsdX1 binds hemoglobin, but not apo-hemoglobin” reports a Kd of 7.33 × 10−6 M for IsdX1 binding holo-hemoglobin, supporting the IsdX1 value. Our copy does not report the claimed 5.5 × 10−8 M value for S. aureus IsdB or establish the comparison with human hemoglobin; searches for IsdB and that value found no matching passage. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Findingown data
S. aureus binds human hemoglobin more effectively than mouse hemoglobin across a range of concentrations.
“These experiments revealed that S. aureus binds hHb more effectively than mHb across a range of concentrations (Figures 1A and S1B).”
- Also stated in: § Abstract · plain
“enhanced ability of S. aureus to bind hemoglobin derived from humans as compared to other mammals”
- Also stated in: § S. aureus preferentially recognizes human hemoglobin · plain
“S. aureus binds hHb more effectively than mHb across a range of concentrations (Figures 1A and S1B).”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
Recombinant IsdB binds human hemoglobin with a stronger affinity (KD 5.5 × 10−8 M) than mouse hemoglobin (KD 9.8 × 10−7 M).
“the KD of the rIsdB-hHb interaction (5.5 × 10−8 M) is significantly stronger than the KD of the rIsdB-mHb interaction (9.8 × 10−7 M).”
Quote in the paperSubstantial claim - Findingown data
S. aureus does not differentiate between human and mouse hemoglobin under iron-replete conditions that prevent isdB expression.
“S. aureus do not differentiate between hHb and mHb when grown under iron-replete conditions that prohibit isdB expression (Figure S4).”
Quote in the paperSubstantial claim - Findingown data
The enhanced growth of S. aureus on human hemoglobin depends on IsdB.
“The enhanced growth of S. aureus in the presence of hHb is dependent on IsdB, as indicated by ΔisdB exhibiting similar growth rates on either hHb or mHb (Figure 2B and S3).”
Quote in the paperSubstantial claim - Findingown data
αHβA mice expressing human hemoglobin are more susceptible to systemic S. aureus infection than wild-type mice.
“αHβA mice were more efficiently colonized as compared to wildtype animals (Figure 3, top).”
- Also stated in: § Abstract · plain
“increased susceptibility of hHb expressing mice to systemic staphylococcal infection.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
S. lugdunensis, S. simulans, and C. diphtheriae show a preference for human hemoglobin similar to S. aureus.
“Staphylococcus lugdunensis, Staphylococcus simulans and Corynebacterium diphtheriae displayed a preference for hHb similar to S. aureus (Figure 4D).”
Quote in the paperNot a substantial claim - Findingown data
IsdB mutants of clinically relevant USA300 and laboratory strains RN4220 and RN6390 lose the increased binding of human hemoglobin.
“Isogenic ΔisdB mutants of clinically relevant USA300 and the common laboratory strains RN4220 and RN6390 lost the ability to bind increased quantities of hHb as observed with strain Newman (Figures 4B and 1A).”
Quote in the paperSubstantial claim - Findingown data
Many organisms without hemoglobin receptors, including E. coli DH5α, S. haemolyticus, S. epidermidis, and Shigella flexneri, cannot proliferate with either human or mouse hemoglobin.
“Many organisms that do not express hemoglobin receptors were unable to proliferate in the presence of either hHb or mHb, including Escherichia coli DH5α, Staphylococcus haemolyticus, Staphylococcus epidermidis and Shigella flexneri (data not shown).”
Quote in the paperNot a substantial claim - Findingown data
A. baumannii, P. aeruginosa, B. anthracis, and B. cereus utilize mouse and human hemoglobin with equal efficiency.
“Acinetobacter baumannii, Pseudomonas aeruginosa, Bacillus anthracis and Bacillus cereus utilized mHb and hHb with equal efficiency.”
Quote in the paperSubstantial claim - Findingown data
S. aureus grows better with human hemoglobin than mouse hemoglobin as the sole iron source.
“S. aureus supplemented with mHb displayed a significant delay in growth as compared to hHb supplementation (Figure 2A and S3).”
- Also stated in: § S. aureus has evolved to acquire nutrient iron from hHb more efficiently than from mHb · plain
“Growth around disks containing hHb was observed by 24 hours and continued to expand over the course of the experiment. In contrast, growth was not detectable around the mHb containing disc until approximately 72 hours after inoculation (Figure 2C).”
Quote in the paperSubstantial claim - Also stated in: § S. aureus has evolved to acquire nutrient iron from hHb more efficiently than from mHb · plain
- Findingown data
The increased binding of human hemoglobin by S. aureus depends on the IsdB receptor.
“Increased specificity for human hemoglobin (hHb) translates into an improved ability to acquire iron and is entirely dependent on the staphylococcal hemoglobin receptor IsdB.”
- Also stated in: § S. aureus preferentially recognizes human hemoglobin · plain
“S. aureus ΔisdB fails to bind increased quantities of hHb compared to mHb and this phenotype is fully complemented by providing a full length copy of isdB in trans (Figures 1B,C and S1B).”
Quote in the paperSubstantial claim - Also stated in: § S. aureus preferentially recognizes human hemoglobin · plain
- Findingown data
Disk diffusion assays show increased proliferation with human hemoglobin as sole iron source compared to mouse hemoglobin for all tested S. aureus strains.
“disk diffusion assays demonstrated increased proliferation using hHb as a sole iron source as compared to mHb for all tested S. aureus strains (Figure 4C).”
Quote in the paperSubstantial claim - Interpretationown data
The preferential binding of human hemoglobin to the S. aureus cell wall is achieved through a stronger interaction with IsdB.
“This result indicates that the preferential binding of hHb to the cell wall of S. aureus is achieved through a stronger interaction with the Hb receptor IsdB.”
Quote in the paperSubstantial claim - Interpretationown data
IsdB-dependent use of human hemoglobin as an iron source is conserved across the S. aureus isolates tested.
“These results demonstrate that the preferential utilization of hHb as an iron source by IsdB is conserved among tested S. aureus isolates.”
- Also stated in: § DISCUSSION · boosted
“Importantly, all tested clinically relevant strains displayed increased iron acquisition from hHb.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · boosted
- Interpretationown data
In αHβA mice, the greater vulnerability to systemic S. aureus infection requires IsdB-mediated hemoglobin binding.
“The presence of human hemoglobin does not affect infection by ΔisdB as demonstrated by the similar susceptibility of wildtype and αHβA mice to ΔisdB (Figure 3, bottom). Thus, the increased susceptibility of αHβA mice to systemic S. aureus infection is fully dependent on hemoglobin binding by IsdB.”
Quote in the paperSubstantial claim - Interpretationown data
S. aureus has evolved to bind human hemoglobin through IsdB more efficiently than mouse hemoglobin.
“These results demonstrate that S. aureus has evolved to bind hHb through IsdB with increased efficiency compared to mHb.”
- Also stated in: § S. aureus preferentially recognizes human hemoglobin · hedged
“The hHb preference of S. aureus is evident amongst hemoglobins from a variety of animal species suggesting that S. aureus has evolved to most efficiently recognize hemoglobin from its human host (Figure S1C).”
Quote in the paperSubstantial claim - Also stated in: § S. aureus preferentially recognizes human hemoglobin · hedged
- Premisecitation
Only a small number of humanized mice have been made that rely on non-immune host factors.
“To date, few humanized mouse models have been established that exploit non-immune host factors (Johansson et al., 2003; Lecuit et al., 2001; Sun et al., 2004).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationreasoning
It is possible to create humanized mice that take advantage of what bacteria need to grow.
“Moreover, these findings demonstrate that humanized mouse models can be created that exploit the nutrient requirements of bacterial pathogens.”
Quote in the paperSubstantial claim- Rests on an assumption: The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
- Interpretationown data
Human hemoglobin is a factor that impacts host susceptibility to S. aureus through its interaction with IsdB.
“Herein, we demonstrate that human hemoglobin is a factor that impacts the host susceptibility to S. aureus through its interaction with the hemoglobin receptor IsdB.”
Quote in the paperSubstantial claim- Rests on an assumption: The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
- Interpretationreasoning
αHβA mice are an improved murine model for studies into staphylococcal infection pathogenesis.
“we have established αHβA mice as an improved murine model for studies into the pathogenesis of staphylococcal infections.”
Quote in the paperSubstantial claim- Rests on an assumption: The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
- Interpretationreasoning
S. aureus IsdB is optimized to bind human hemoglobin in order to acquire iron and colonize humans.
“This supports the hypothesis that S. aureus IsdB is optimized to bind hHb in order to acquire iron and colonize humans.”
Quote in the paperSubstantial claim- Rests on an assumption: The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
- Premisenone given
Because mice and humans differ inherently, mouse infection models are imperfect models of human disease.
“However, due to inherent differences between mice and humans, murine infection models do not perfectly recapitulate human disease.”
Quote in the paperSubstantial claim - Interpretationreasoning
The findings add human hemoglobin expressing mice to the list of humanized animals valuable for modeling infection.
“Our findings add the human hemoglobin expressing mouse to the list of humanized animals that are valuable tools for modeling infection.”
Quote in the paperSubstantial claim- Rests on an assumption: The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
- Premisecitation
S. aureus lyses erythrocytes through secretion of hemolytic toxins.
“S. aureus lyses erythrocytes through the secretion of hemolytic toxins (Torres et al., 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Torres et al., 2010 source
- May combine two claims. 13
- Classified as probably not a substantial claim. 6
May combine two claims.
PremisecitationBinding hemoglobin is needed for heme-iron uptake during infection and is important in S. aureus disease.
“Hemoglobin binding is a prerequisite for heme-iron acquisition during infection and as such, plays a critical role during S. aureus infection (Pishchany et al., 2009; Torres et al., 2006).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites Pishchany et al., 2009 source
- cites Torres et al., 2006 source
The Discussion reports that IsdB-mediated hemoglobin binding is required for growth on hemoglobin as the sole iron source in vitro and contributes to virulence in a mouse infection model. It does not establish that hemoglobin binding is a prerequisite for heme-iron acquisition during infection; that acquisition pathway is presented as a proposed model. (LLM, conf=0.85)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationMurine infection studies have shown that the Isd system matters for iron uptake and S. aureus virulence.
“The importance of the Isd system to iron acquisition and staphylococcal pathogenicity has been demonstrated using murine models of infection (Cheng et al., 2009; Mazmanian et al., 2000; Pishchany et al., 2009; Torres et al., 2006).”
Quote in the paperSubstantial claim3 of 3 sources checked- cites Cheng et al., 2009 source
- cites Mazmanian et al., 2000 source
The Results report that an S. aureus sortase mutant was markedly less virulent than the wild type in mouse infection models. But these experiments test sortase and surface-protein display, not the Isd system or iron acquisition; the cited paper does not establish the claim's Isd-specific point. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites Pishchany et al., 2009 source
May combine two claims.
PremisecitationThe entire process of hemoglobin binding, heme extraction, passage through the cell envelope, and degradation to release iron is carried out by the Isd system, which is up-regulated during iron starvation.
“This entire process is carried out by members of the Iron-regulated Surface Determinant system (Isd), which are up-regulated during conditions of iron starvation (Mazmanian et al., 2003; Muryoi et al., 2008; Pishchany et al., 2009; Reniere and Skaar, 2008; Reniere et al., 2007; Reniere et al., 2010; Skaar et al., 2004; Torres et al., 2006; Zhu et al., 2008).”
Quote in the paperNot a substantial claim1 of 3 sources checkedMay combine two claims.
Findingown dataTotal hemoglobin concentration does not differ between αHβA and wild-type animals, so susceptibility differences are not due to hemoglobin abundance.
“total Hb concentration does not differ between αHβA and wild type animals therefore variations in susceptibility are not due to hemoglobin abundance (data not shown).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAn IsdB mutant with alanine replacing conserved tyrosine 165 eliminates hemoglobin binding, indicating that Y165 is critical for hemoglobin recognition.
“Cell wall expression of a mutant version of isdB containing an alanine substitution in place of the absolutely conserved tyrosine residue at position 165 eliminates hemoglobin binding, establishing this residue as being critical for hemoglobin recognition by IsdB (Figure 1D).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe enhanced specificity of S. aureus for human hemoglobin translates into increased colonization and establishes αHβA mice as a humanized model with increased susceptibility to S. aureus infection.
“These results demonstrate that the enhanced specificity of S. aureus for hHb translates into increased colonization and establishes αHβA as a humanized mouse that exhibits increased susceptibility to S. aureus infections.”
Quote in the paperSubstantial claim- Rests on an assumption: The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
May combine two claims.
Interpretationown dataS. aureus has evolved to acquire nutrient iron from human hemoglobin more efficiently than from mouse hemoglobin, mediated by IsdB.
“These findings demonstrate that S. aureus has evolved to acquire nutrient iron from hHb more efficiently than from mHb, and the enhanced recognition of hHb is mediated by the hemoglobin receptor IsdB.”
Quote in the paperSubstantial claim- Rests on an assumption: The in vitro binding and growth assays with purified hemoglobin reflect the interaction of S. aureus with hemoglobin during infection.
May combine two claims.
Premiseown dataThe primary amino acid sequence of hemoglobin differs across species, with variation primarily in surface-exposed residues likely recognized by IsdB.
“Notably, the primary amino acid sequence of hemoglobin differs across species and variation within hemoglobin primarily localizes to surface exposed residues that are likely recognized by IsdB (Figure S1A).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA broad range of bacterial pathogens can use hemoglobin as an iron source.
“Importantly, many bacterial pathogens utilize hemoglobin as an iron source; therefore human hemoglobin expressing mice may be valuable for studies into a variety of infectious diseases (Crosa et al., 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Crosa et al., 2004
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
PremisecitationAs a defense against infection, vertebrates restrict nutrients that microbes need to multiply, a process called nutritional immunity.
“Vertebrates sequester nutrients required for microbial multiplication as a defense against infection in a process termed nutritional immunity (Bullen, 1981).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bullen, 1981 source
May combine two claims.
Interpretationown dataSome bacterial pathogens preferentially use human hemoglobin as an iron source, whereas others treat human and mouse hemoglobin alike.
“These results demonstrate that the preferential utilization of hHb as an iron source is conserved across some bacterial pathogens while others do not discriminate between hHb and mHb.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe Vanderbilt University institutional animal care and use committee approved the animal experiments.
“Animal experiments were approved by the institutional animal care and use committee of Vanderbilt University.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataBacteria that primarily associate with humans (S. aureus, S. lugdunensis, S. simulans, C. diphtheriae) display preference for human over mouse hemoglobin, whereas environmental bacteria that infect numerous hosts (A. baumannii, P. aeruginosa, B. anthracis, B. cereus) grow comparably on both.
“Notably, bacteria that primarily associate with humans (S. aureus, S. lugdunensis, S. simulans, C. diphtheria) display preference for hHb over mHb, whereas environmental bacteria that infect numerous hosts (A. baumannii, P. aeruginosa, B. anthracis and B. cereus ) grow at comparable levels on hHb and mHb.”
Quote in the paperSubstantial claim- Rests on an assumption: The bacterial species tested are representative of their host association categories.
May combine two claims.
Interpretationown dataIsdB's strong affinity for human hemoglobin allows S. aureus to use it efficiently as an iron source, which leads to greater colonization and disease.
“The significant affinity of IsdB for human hemoglobin permits the efficient utilization of hHb as an iron source leading to increased colonization and disease.”
Quote in the paperSubstantial claim- Rests on an assumption: The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
- Rests on an assumption: The in vitro binding and growth assays with purified hemoglobin reflect the interaction of S. aureus with hemoglobin during infection.
Classified as probably not a substantial claim.
PremisecitationIron is vital to the host-pathogen interaction.
“Iron is one such nutrient that is vital to the host-pathogen interaction (Crosa et al., 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Crosa et al., 2004
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHemoglobin is the largest iron reservoir in vertebrates.
“The most abundant source of iron within vertebrates is hemoglobin (Drabkin, 1951).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Drabkin, 1951 source
Classified as probably not a substantial claim. May combine two claims.
PremisereasoningBacterial pathogens must free intracellular iron and outcompete host iron-binding proteins in order to multiply inside vertebrates.
“In order to grow within vertebrates, bacterial pathogens must liberate intracellular iron and compete with host iron-sequestering proteins.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThis process is required for pathogenesis, as shown by decreased proliferation of isdB-inactivated S. aureus strains in murine models.
“This process is required for pathogenesis as demonstrated by the decreased proliferation of S. aureus strains inactivated for isdB in murine models.”
Quote in the paperSubstantial claim
The paper relies on this without support.
αHβA mice express approximately equal levels of human and mouse hemoglobin.
“Importantly, αHβA mice express approximately equal levels of both hHb and mHb suggesting that the effects observed here may underestimate the contribution of hHb to staphylococcal infection in humans.”
The paper relies on this without support.
The αHβA mouse model's human hemoglobin expression is representative of human hemoglobin's role in human S. aureus infection.
“we have established αHβA mice as an improved murine model for studies into the pathogenesis of staphylococcal infections.”
The paper relies on this without support.
The in vitro binding and growth assays with purified hemoglobin reflect the interaction of S. aureus with hemoglobin during infection.
“These results demonstrate that the enhanced specificity of S. aureus for hHb translates into increased colonization and establishes αHβA as a humanized mouse that exhibits increased susceptibility to S. aureus infections.”
The paper relies on this without support.
The bacterial species tested are representative of their host association categories.
“Notably, bacteria that primarily associate with humans (S. aureus, S. lugdunensis, S. simulans, C. diphtheria) display preference for hHb over mHb, whereas environmental bacteria that infect numerous hosts (A. baumannii, P. aeruginosa, B. anthracis and B. cereus ) grow at comparable levels on hHb and mHb.”
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 Staphylococcus aureus Isd system has evolved to utilize human hemoglobin preferentially over hemoglobin from other species.
“Of note, S. aureus the Isd system has evolved to utilize human hemoglobin preferentially over hemoglobin from other species.”
From Iron in infection and immunity (2013) · cites this paper as Pishchany et al., 2010
Transgenic mice expressing human hemoglobin alleles are more susceptible to Staphylococcus aureus infection.
“Accordingly, transgenic mice expressing human hemoglobin alleles are more susceptible to S. aureus infection (Pishchany et al., 2010).”
From Iron in infection and immunity (2013) · cites this paper as Pishchany et al., 2010
Mice expressing human hemoglobin are more susceptible to S. aureus infection, with increased colony recovery from infected organs.
“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.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [118]
This virulence increase depends on IsdB, because isdB mutants proliferate similarly in wild-type and human hemoglobin mice.
“This increase in virulence is dependent on IsdB, as S. aureus mutants inactivated for isdB proliferate to similar levels in both wild type mice and mice expressing human hemoglobin.”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [61]
IsdB has significantly higher affinity for human hemoglobin than for mouse hemoglobin.
“This is supported by the observation that the affinity of IsdB for human hemoglobin is significantly higher than the affinity for mouse hemoglobin.”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [61]
S. aureus burden is increased by an order of magnitude in hearts and livers of mice expressing a human hemoglobin transgene after systemic infection.
“In keeping with this, the burden of S. aureus is increased by an order of magnitude in the hearts and livers of mice expressing a human hemoglobin transgene following systemic infection (61).”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [61]
Human hemoglobin is more readily used as an iron source by S. aureus in culture.
“Moreover, human hemoglobin is more readily utilized as an iron source by S. aureus in culture.”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [61]
Neutrophils, the primary target cells for pvl, are highly insensitive to this pore-forming toxin in mice.
“The importance of pvl in S. aureus infections is mostly controversial mainly due to the limitations of the widely used murine models [65], [66], [67], [68], [69], as neutrophils, the primary target cells for pvl, are highly insensitive to this pore-forming toxin in mice [68], [70], [71].”
From Interactions of Methicillin Resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in Polymicrobial Wound Infection (2013) · cites this paper as [68]
S. aureus cannot fully utilize iron from murine hemoglobin.
“In addition, S. aureus cannot fully utilize iron from murine hemoglobin [68], [70], [71].”
From Interactions of Methicillin Resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in Polymicrobial Wound Infection (2013) · cites this paper as [68]
The growth of microbes is critically dependent on iron, which might serve as a further explanation for the detrimental effects of hemolysis.
“Moreover, the finding that the growth of microbes is critically dependent on iron might serve as a further explanation for the detrimental effects of hemolysis [32,33].”
From Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome (2012) · cites this paper as [32]
Staphylococcus aureus strongly prefers human hemoglobin over mouse hemoglobin, and this preference correlates with growth in murine infection models.
“Elegant work by Pishchany et al. demonstrated that the Gram-positive bacterium Staphylococcus aureus exhibits strong preference for human hemoglobin over mouse hemoglobin, which correlates with bacterial growth in murine models of infection [75].”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [75]
Bacterial pathogens need heme to cause disease.
“Bacterial pathogens require the iron-containing cofactor heme to cause disease.”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [86]
For S. aureus, reliance on heme acquisition during infection has been well established, and heme biosynthesis is vital to cause disease in murine models of infection.
“For S. aureus, whose reliance on heme acquisition during infection has been well established, it is now clear that heme biosynthesis is vital to cause disease in murine models of infection [84–86].”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [86]
Isd-mediated heme acquisition is vital to the virulence of S. aureus.
“Isd-mediated heme acquisition is vital to the virulence of S. aureus.”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [86]
Mutants lacking components of the Isd system are highly defective in pathogenesis, highlighting the importance of heme acquisition to staphylococcal disease.
“Mutants lacking components of the Isd system are highly defective inpathogenesis, highlighting the importance of heme acquisition to staphylo-coccal disease [84–86,108,120,123,124].”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [86]
Transgenic mice expressing human Hb are more susceptible to S. aureus disease.
“transgenic mice expressing human Hb are more susceptible to S. aureus disease [86].”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [86]
S. aureus IsdB exhibits species specificity and more efficiently utilizes human Hb relative to mouse Hb.
“the Hb-binding IsdB of S. aureus exhibits species specificity and more efficiently utilizes human Hb relative to mouse Hb [86].”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [86]
Inactivation of isdA, isdB, isdC, isdG, or isdI reduces bacterial proliferation in the host.
“Consistent with the importance of heme-iron acquisition to the pathogenesis of staphylococcal infections, inactivation of isdA , isdB , isdC , isdG, or isdI reduces bacterial proliferation within the host [3, 4, 21, 27 -29].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [29]
IsdB binds human hemoglobin with higher affinity than hemoglobin from other species.
“We have previously found that IsdB binds human hemoglobin with a higher af fi nity than hemoglobin from other species”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [29]
Mice expressing human hemoglobin (αHβA) are more susceptible to S. aureus infection.
“and that mice expressing human hemoglobin ( α H β A ) are more susceptible to S. aureus infection [29, 32].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [29]
S. aureus strains without isdB show reduced colonization in murine infection models.
“S. aureus strains lacking isdB are reduced for colonization in murine models of infection [3, 4, 27 -29].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [29]
S. aureus binds human hemoglobin more specifically than mouse hemoglobin.
“Due to the increased speci fi city of S. aureus for human hemoglobin compared to mouse hemoglobin, we have established transgenic mice expressing human hemoglobin ( α H β A ) as an enhanced model of S. aureus infection [29, 32].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [29]
IsdB from both species prefers human hemoglobin over mouse hemoglobin.
“IsdB from both species displays a preference for human hemoglobin over mouse hemoglobin, which has important implications for the evolution of these organisms to infect their primary host [29, 42].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [29]
S. aureus evolved to use hemoglobin as its preferred iron source during infection, and its IsdB hemoglobin-binding protein evolved to preferentially bind human hemoglobin over hemoglobin from other animals.
“S. aureus evolved to use hemoglobin as its preferred iron source in infection, and its IsdB hemoglobin-binding protein evolved to preferentially bind human hemoglobin over hemoglobin from other animals (109, 123).”
From Transition Metals and Virulence in Bacteria (2016) · cites this paper as [109]
IsdB exhibits low affinity for murine hemoglobin compared to human hemoglobin.
“One such factor is the staphylococcal hemoglobin receptor IsdB, which exhibits low affinity for murine hemoglobin as compared to human hemoglobin (Pishchany et al., 2010).”
From Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes (2015) · cites this paper as Pishchany et al., 2010
Transgenic mice expressing human hemoglobin are more susceptible to S. aureus infection than wildtype mice, demonstrating pathophysiological relevance.
“Transgenic mice that express human hemoglobin are more susceptible to S. aureus infection than wildtype mice demonstrating the pathophysiological relevance of these findings.”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [47]
S. aureus IsdB binds human hemoglobin more efficiently than hemoglobin from other animal species, with a KD of 5.5 × 10−8 for human hemoglobin versus 9.8 × 10−7 for mouse hemoglobin.
“the S. aureus hemoglobin receptor IsdB binds human hemoglobin more efficiently than hemoglobin from other animal species [47]. In fact the KD of the interaction between recombinant IsdB and human hemoglobin is 5.5 × 10−8 as compared to a KD of 9.8 × 10−7 for the interaction between IsdB and mouse hemoglobin.”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [47]
IsdB is surface exposed and important during infection, making it a viable vaccine candidate.
“The hemoglobin binding protein IsdB plays a pivotal role during infection and is surface exposed establishing this protein as a viable vaccine candidate [47].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [47]
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Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
Cites a retracted work: 10.1096/fj.09-135467
MajorThe cited work was retracted on 2010-02-01 (notice 10.1096/fj.09-135467err), before this paper was published (2010-12). Its authors could have known.
Cited work 10.1096/fj.09-135467 · retracted 2010-02-01 · notice 10.1096/fj.09-135467err · this paper published 2010-12
“The importance of the Isd system to iron acquisition and staphylococcal pathogenicity has been demonstrated using murine models of infection (Cheng et al., 2009; Mazmanian et al., 2000; Pishchany et al., 2009; Torres et al., 2006).”
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“The importance of the Isd system to iron acquisition and staphylococcal pathogenicity has been demonstrated using murine models of infection (Cheng et al., 2009; Mazmanian et al., 2000; Pishchany et al., 2009; Torres et al., 2006).”
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A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier
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BackgroundStaphylococcal Coagulase: Mode of Action and Antigenicity
Duthie, E. S., & Lorenz, L. (1952) · Microbiology · doi:10.1099/00221287-6-1-2-95 · Cited by 623 · cited 5× · see citing works
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BackgroundPassage of Heme-Iron Across the Envelope of <i>Staphylococcus aureus</i>
Mazmanian, S. K., Skaar, E. P., Gaspar, A. H., Humayun, M., Gornicki, P., Jelenska, J., Joachmiak, A., Missiakas, D. M., & Schneewind, O. (2003) · Science · doi:10.1126/science.1081147 · Cited by 593 · cited 5× · see citing works
“Purification of recombinant IsdB has been previously described (Mazmanian et al., 2003).”
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“The importance of the Isd system to iron acquisition and staphylococcal pathogenicity has been demonstrated using murine models of infection (Cheng et al., 2009; Mazmanian et al., 2000; Pishchany et al., 2009; Torres et al., 2006).”
BackgroundIron-Source Preference of <i>Staphylococcus aureus</i> Infections
Skaar, E. P., Humayun, M., Bae, T., DeBord, K. L., & Schneewind, O. (2004) · Science · doi:10.1126/science.1099930 · Cited by 440 · cited 4× · see citing works
“aureus with iron necessary for growth (Skaar et al., 2004; Torres et al., 2006).”
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“These findings raise the exciting possibility that human hemoglobin polymorphisms may have implications regarding individual susceptibility to bacterial infections (Hardison et al., 2002).”
BackgroundPlasminogen is a critical host pathogenicity factor for group A streptococcal infection
Sun, H., Ringdahl, U., Homeister, J. W., Fay, W. P., Engleberg, N. C., Yang, A. Y., Rozek, L. S., Wang, X., Sjöbring, U., & Ginsburg, D. (2004) · Science · doi:10.1126/science.1101245 · Cited by 408 · cited 1× · see citing works
“To date, few humanized mouse models have been established that exploit nonimmune host factors (Johansson et al., 2003; Lecuit et al., 2001; Sun et al., 2004).”
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“Iron is one such nutrient that is vital to the host-pathogen interaction (Crosa et al., 2004).”
Background<i>Staphylococcus aureus</i> IsdB Is a Hemoglobin Receptor Required for Heme Iron Utilization
Torres, V. J., Pishchany, G., Humayun, M., Schneewind, O., & Skaar, E. P. (2006) · Journal of Bacteriology · doi:10.1128/jb.01335-06 · Cited by 302 · cited 9× · see citing works
“Human Hemoglobin Exacerbates S. aureus Infection in a Murine Model Hemoglobin binding is a prerequisite for heme-iron acquisition during infection and, as such, plays a critical role duringS. aureus infection (Pishchany et al., 2009; Torres et al., 2006).”
BackgroundInfluentialSelf-citationMethicillin-resistant–<i>Staphylococcus aureus</i>Hospitalizations, United States
Kuehnert, M. J., Hill, H. A., Kupronis, B. A., Tokars, J. I., Solomon, S. L., & Jernigan, D. B. (2005) · Emerging Infectious Diseases · doi:10.3201/eid1106.040831 · Cited by 287 · cited 2× · see citing works
“aureus is also capable of breaching these sites of initial colonization leading to significant morbidity and mortality (Klevens et al., 2007; Kuehnert et al., 2005).”
BackgroundHumanized Mice for Modeling Human Infectious Disease: Challenges, Progress, and Outlook
Legrand, N., Ploß, A., Balling, R., Becker, P. D., Borsotti, C., Brezillon, N., Debarry, J., de Jong, Y. P., Deng, H., Santo, J. P. D., et al. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.06.006 · Cited by 207 · cited 1× · see citing works
“To improve on this shortcoming, significant effort has been devoted to the development of humanized mouse models that more accurately reflect human disease (Legrand et al., 2009; Shultz et al., 2007).”
BackgroundJohansson, L., Rytkönen, A., Bergman, P., Albiger, B., Källström, H., Hökfelt, T., Agerberth, B., Cattaneo, R., & Jonsson, A.-B. (2003) · Science · doi:10.1126/science.1086476 · Cited by 182 · cited 1× · see citing works
“To date, few humanized mouse models have been established that exploit nonimmune host factors (Johansson et al., 2003; Lecuit et al., 2001; Sun et al., 2004).”
BackgroundTorres, V. J., Attia, A. S., Mason, W. J., Hood, M. I., Corbin, B. D., Beasley, F. C., Anderson, K. L., Stauff, D. L., McDonald, W. H., Zimmerman, L. J., et al. (2010) · Infection and Immunity · doi:10.1128/iai.01423-09 · Cited by 169 · cited 2× · see citing works
“aureus lyses erythrocytes through the secretion of hemolytic toxins (Torres et al., 2010).”
BackgroundSelf-citationMuryoi, N., Tiedemann, M. T., Pluym, M., Cheung, J., Heinrichs, D. E., & Stillman, M. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802171200 · Cited by 144 · cited 2× · see citing works
“This entire process is carried out by members of the iron-regulated surface determinant system (Isd), which are upregulated during conditions of iron starvation (Mazmanian et al., 2003; Muryoi et al., 2008; Pishchany et al., 2009; Reniere and Skaar, 2008; Reniere et al., 2007, 2010; Skaar et al., 2004; Torres et al.,…”
BackgroundBacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin
Maresso, A. W., Garufi, G., & Schneewind, O. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000132 · Cited by 144 · cited 2× · see citing works
“3 3 10 6 M) (Maresso et al., 2008).”
BackgroundInfluentialThe IsdG‐family of haem oxygenases degrades haem to a novel chromophore
Reniere, M. L., Ukpabi, G. N., Harry, S. R., Stec, D. F., Krull, R., Wright, D. W., Bachmann, B. O., Murphy, M. E., & Skaar, E. P. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07076.x · Cited by 139 · cited 4× · see citing works
“In order to test whether the increased specificity for hHb benefits S. aureus during infection, we examined the susceptibility of transgenic aHbA mice that express normal adult human hemoglobin to systemic staphylococcal infection (Romero et al., 2004).”
BackgroundMethodInfluentialSelf-citationMetabolism of the hemin chromoproteins
Drabkin, D. L. (1951) · Physiological Reviews · doi:10.1152/physrev.1951.31.4.345 · Cited by 132 · see citing works
Zhu, H., Xie, G., Liu, M., Olson, J. S., Fabian, M., Dooley, D. M., & Lei, B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801466200 · Cited by 127 · cited 1× · see citing works
“…of the iron-regulated surface determinant system (Isd), which are upregulated during conditions of iron starvation (Mazmanian et al., 2003; Muryoi et al., 2008; Pishchany et al., 2009; Reniere and Skaar, 2008; Reniere et al., 2007, 2010; Skaar et al., 2004; Torres et al., 2006; Zhu et al., 2008).”
BackgroundTransferrin binding in Staphylococcus aureus: involvement of a cell wall‐anchored protein
Taylor, J. M., & Heinrichs, D. E. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02850.x · Cited by 116 · cited 1× · see citing works
“RN6390 DisdB has been described previously (Taylor and Heinrichs, 2002).”
Intracellular metalloporphyrin metabolism in Staphylococcus aureus
Reniere, M. L., Torres, V. J., & Skaar, E. P. (2007) · BioMetals · doi:10.1007/s10534-006-9032-0 · Cited by 102 · cited 1× · see citing works
“…of the iron-regulated surface determinant system (Isd), which are upregulated during conditions of iron starvation (Mazmanian et al., 2003; Muryoi et al., 2008; Pishchany et al., 2009; Reniere and Skaar, 2008; Reniere et al., 2007, 2010; Skaar et al., 2004; Torres et al., 2006; Zhu et al., 2008).”
BackgroundSelf-citationMetabolism of the Hemin Chromoproteins
Drabkin, D. L. (1952) · Physiological Reviews · doi:10.1152/physrev.1952.32.4.523-s · Cited by 97 · cited 1× · see citing works
“The most abundant source of iron within vertebrates is hemoglobin (Drabkin, 1951).”
Background<i>Staphylococcus aureus</i> haem oxygenases are differentially regulated by iron and haem
Reniere, M. L., & Skaar, E. P. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06363.x · Cited by 86 · cited 2× · see citing works
“…of the iron-regulated surface determinant system (Isd), which are upregulated during conditions of iron starvation (Mazmanian et al., 2003; Muryoi et al., 2008; Pishchany et al., 2009; Reniere and Skaar, 2008; Reniere et al., 2007, 2010; Skaar et al., 2004; Torres et al., 2006; Zhu et al., 2008).”
BackgroundSelf-citationPishchany, G., Dickey, S. E., & Skaar, E. P. (2009) · Infection and Immunity · doi:10.1128/iai.01531-08 · Cited by 77 · cited 7× · see citing works
“Human Hemoglobin Exacerbates S. aureus Infection in a Murine Model Hemoglobin binding is a prerequisite for heme-iron acquisition during infection and, as such, plays a critical role duringS. aureus infection (Pishchany et al., 2009; Torres et al., 2006).”
BackgroundInfluentialSelf-citationDryla, A., Hoffmann, B., Gelbmann, D., Giefing, C., Hanner, M., Meinke, A., Anderson, A. S., Koppensteiner, W., Konrat, R., von Gabain, A., et al. (2007) · Journal of Bacteriology · doi:10.1128/jb.01366-06 · Cited by 73 · cited 1× · see citing works
“Notably, this calculated affinity for the interaction of IsdB and hHb is consistent Cell Host & with previously published findings (Dryla et al., 2007).”
ResultWeems, J. J. (2001) · Postgraduate Medicine · doi:10.3810/pgm.2001.10.1042 · Cited by 62 · see citing works
Romero, J. R., Suzuka, S. M., Nagel, R. L., & Fabry, M. E. (2004) · Blood · doi:10.1182/blood-2003-01-0237 · Cited by 25 · cited 2× · see citing works
“In order to test whether the increased specificity for hHb benefits S. aureus during infection, we examined the susceptibility of transgenic aHbA mice that express normal adult human hemoglobin to systemic staphylococcal infection (Romero et al., 2004).”
BackgroundMethodSelf-citationHigh oxygen environment during pregnancy rescues sickle cell anemia mice from prenatal death
Lin, Y., Chang, J. C., Lu, R., & Kan, Y. W. (2008) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2007.12.002 · Cited by 9 · cited 1× · see citing works
“However, hHb knockin mice are notoriously difficult to breed and are therefore unsuitable for infection models, which require high numbers of subjects in order to evaluate statistical significance (Ye et al., 2008).”
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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 1,534 · see citing works
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 · see citing works
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 · see citing works
“Accordingly, transgenic mice expressing human hemoglobin alleles are more susceptible to S. aureus infection (Pishchany et al., 2010).”
BackgroundSelf-citationTransition Metals and Virulence in Bacteria
Palmer, L. D., & Skaar, E. P. (2016) · Annual Review of Genetics · doi:10.1146/annurev-genet-120215-035146 · Cited by 449 · see citing works
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“aureus infections is mostly controversial mainly due to the limitations of the widely used murine models [65,66,67,68,69], as neutrophils, the primary target cells for pvl, are highly insensitive to this pore-forming toxin in mice [68,70,71].”
BackgroundMolecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition
Hammer, N. D., & Skaar, E. P. (2011) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090110-102851 · Cited by 379 · see citing works
“aureus is increased by an order of magnitude in the hearts and livers of mice expressing a human hemoglobin transgene following systemic infection (61).”
BackgroundSelf-citationHeme Synthesis and Acquisition in Bacterial Pathogens
Choby, J. E., & Skaar, E. P. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.03.018 · Cited by 343 · see citing works
Self-citationScenery of Staphylococcus Implant Infections in Orthopedics
Montanaro, L., Speziale, P., Campoccia, D., Ravaioli, S., Cangini, I., Pietrocola, G., Giannini, S., & Arciola, C. R. (2011) · Future Microbiology · doi:10.2217/fmb.11.117 · Cited by 368 · see citing works
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Sortase enzymes in Gram‐positive bacteria
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“…haemoglobin such that murine models of infection may underestimate the pathogenic importance of the Sa-SrtB anchored IsdC protein and other iron-regulated surface determinant proteins that participate in the capture of haem-iron from human haemoglobin during infections (Pishchany et al., 2010).”
BackgroundRecent developments in understanding the iron acquisition strategies of gram positive pathogens
Sheldon, J. R., & Heinrichs, D. E. (2015) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuv009 · Cited by 272 · see citing works
“The preference of St. lugdunensis for human hemoglobin may be reflective of its exclusivity as a human pathogen, and highlights the challenges in developing a suitable model for assessing its in vivo survival and virulence (Pishchany et al. 2010; Zapotoczna et al. 2012).”
BackgroundKébaïer, C., Chamberland, R. R., Allen, I. C., Gao, X., Broglie, P. M., Hall, J. D., Jania, C. M., Doerschuk, C. M., Tilley, S. L., & Duncan, J. A. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir846 · Cited by 261 · see citing works
Pantosti, A. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00127 · Cited by 239 · see citing works
“This explains, at least in part, why S. aureus thrives in the presence of human blood and why humans are generally the preferential host for S. aureus (Pishchany et al., 2010).”
BackgroundMedical decision support using machine learning for early detection of late-onset neonatal sepsis
Mani, S., Özdaş, A., Aliferis, C., Varol, H. A., Chen, Q., Carnevale, R. J., Chen, Y., Romano-Keeler, J., Nian, H., & Weitkamp, J.-H. (2013) · Journal of the American Medical Informatics Association · doi:10.1136/amiajnl-2013-001854 · Cited by 196 · see citing works
Mouse models for infectious diseases caused by Staphylococcus aureus
Kim, H. K., Missiakas, D. M., & Schneewind, O. (2014) · Journal of Immunological Methods · doi:10.1016/j.jim.2014.04.007 · Cited by 180 · see citing works
Immunopathogenesis of Staphylococcus aureus pulmonary infection
Parker, D., & Prince, A. S. (2011) · Seminars in Immunopathology · doi:10.1007/s00281-011-0291-7 · Cited by 167 · see citing works
“aureus infection [28].”
A battle for iron: host sequestration and Staphylococcus aureus acquisition
Haley, K. P., & Skaar, E. P. (2012) · Microbes and Infection · doi:10.1016/j.micinf.2011.11.001 · Cited by 157 · see citing works
“aureus IsdB for human hemoglobin translates to a more efficient use of hemoglobin-iron during infection [47].”
BackgroundInfluentialSelf-citationSurface Proteins ofStaphylococcus aureus
Foster, T. J. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.gpp3-0046-2018 · Cited by 160 · see citing works
Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity
Cassat, J. E., & Skaar, E. P. (2012) · Seminars in Immunopathology · doi:10.1007/s00281-011-0294-4 · Cited by 155 · see citing works
“IsdB binds human hemoglobin more readily than murine hemoglobin in vitro, and deletion of isdB abolishes the enhanced virulence of staphylococci infecting mice with human hemoglobin [118].”
BackgroundSelf-citationVaccine review: “Staphyloccocus aureus vaccines: Problems and prospects”
Jansen, K. U., Girgenti, D., Scully, I. L., & Anderson, A. S. (2013) · Vaccine · doi:10.1016/j.vaccine.2013.04.002 · Cited by 151 · see citing works
“Therefore, no preclinical animal model of infection fully recapitulates the natural infectious process in humans, due to differences in host cell proteins, such as hemoglobin [10], and the requirement”
BackgroundFree hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome
Adamzik, M., Hamburger, T., Petrat, F., Peters, J., de Groot, H., & Hartmann, M. (2012) · Critical Care · doi:10.1186/cc11425 · Cited by 137 · see citing works
“Moreover, the finding that the growth of microbes is critically dependent on iron might serve as a further explanation for the detrimental effects of hemolysis [32,33].”
BackgroundLivestock associated MRSA (LA-MRSA) and its relevance for humans in Germany
Cuny, C., Köck, R., & Witte, W. (2013) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2013.02.010 · Cited by 131 · see citing works
Vitko, N. P., Grosser, M. R., Khatri, D., Thurlow, L. R., & Richardson, A. R. (2016) · mBio · doi:10.1128/mbio.00296-16 · Cited by 133 · see citing works
Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy
Barber, M. F., & Elde, N. C. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.09.001 · Cited by 118 · see citing works
“demonstrated that the Gram-positive bacterium Staphylococcus aureus exhibits strong preference for human hemoglobin over mouse hemoglobin, which correlates with bacterial growth in murine models of infection [75].”
BackgroundMechanisms of Hemolysis During Sepsis
Effenberger‐Neidnicht, K., & Hartmann, M. (2018) · Inflammation · doi:10.1007/s10753-018-0810-y · Cited by 122 · see citing works
Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes
Spaan, A. N., Reyes-Robles, T., Badiou, C., Cochet, S., Boguslawski, K. M., Yoong, P., Day, C. J., de Haas, C. J. C., van Kessel, K. P. M., Vandenesch, F., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.08.001 · Cited by 114 · see citing works
“One such factor is the staphylococcal hemoglobin receptor IsdB, which exhibits low affinity for murine hemoglobin as compared to human hemoglobin (Pishchany et al., 2010).”
BackgroundSelf-citationMethicillin-Resistant Staphylococcus aureus Adaptation to Human Keratinocytes
Soong, G., Paulino, F. E., Wachtel, S., Parker, D., Wickersham, M., Zhang, D., Brown, A. O., Lauren, C. T., Dowd, M. L., West, E. S., et al. (2015) · mBio · doi:10.1128/mbio.00289-15 · Cited by 111 · see citing works
“aureus clearance, an important factor in in vivo infection (14), but demonstrate the contribution of the secreted toxins and their effects in promoting staphylococcal clearance by keratinocytes (12, 49).”
BackgroundAbdiche, Y. N., Miles, A., Eckman, J. W., Foletti, D. L., Blarcom, T. J. V., Yeung, Y. A., Pons, J., & Rajpal, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092451 · Cited by 107 · see citing works
Guggenberger, C., Wolz, C., Morrissey, J. A., & Heesemann, J. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002434 · Cited by 100 · see citing works
“species specificity of coagulase and human-specific hemoglobin utilization [17,18]).”
BackgroundOxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering
Fathollahipour, S., Patil, P. S., & Leipzig, N. D. (2018) · Cells Tissues Organs · doi:10.1159/000493162 · Cited by 101 · see citing works
“Additionally, recombinant Hb helps to eliminate the chance of cross-contamination from mammalian donors [Pishchany et al., 2010].”
Marchetti, M., Bei, O. D., Bettati, S., Campanini, B., Kovachka, S., Gianquinto, E., Spyrakis, F., & Ronda, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062145 · Cited by 92 · see citing works
IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus
Pishchany, G., Sheldon, J. R., Dickson, C. F., Alam, M. T., Read, T. D., Gell, D. A., Heinrichs, D. E., & Skaar, E. P. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit817 · Cited by 88 · see citing works
“aureus Hemoglobin Binding Assay Hemoglobin purification and coprecipitation was performed as described elsewhere [29].”
BackgroundMethodSelf-citationMcCarthy, A. J., Witney, A. A., Gould, K. A., Moodley, A., Guardabassi, L., Voß, A., Denis, O., Broens, E. M., Hinds, J., & Lindsay, J. A. (2011) · Genome Biology and Evolution · doi:10.1093/gbe/evr092 · Cited by 89 · see citing works
“Firstly, the isdB gene has recently been shown to bind to human but not mouse hemoglobin (Pishchany et al. 2010).”
BackgroundInfluentialMolecular basis of host specificity in human pathogenic bacteria
Pan, X., Yang, Y., & Zhang, J. (2014) · Emerging Microbes & Infections · doi:10.1038/emi.2014.23 · Cited by 80 · see citing works
Soong, G., Chun, J., Parker, D., & Prince, A. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis244 · Cited by 84 · see citing works
“hemoglobin [8] and mouse models require large intradermal inoculations of bacteria, obviating the relevance of the physical and immunological barrier properties of normal human skin [4].”
BackgroundHazenbos, W. L. W., Kajihara, K. K., VANDLEN, R. L., Morisaki, J. H., Lehar, S. M., Kwakkenbos, M. J., Beaumont, T., Bakker, A. Q., Phung, Q. T., Swem, L. R., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003653 · Cited by 76 · see citing works
“aureus and host factors, to be specific for human and not occur in mice [30,31].”
Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element
Benson, M. A., Ohneck, E. A., Ryan, C., Alonzo, F., Smith, H., Narechania, A., Kolokotronis, S., Satola, S. W., Uhlemann, A., Sebra, R., et al. (2014) · Molecular Microbiology · doi:10.1111/mmi.12682 · Cited by 84 · see citing works
“Lastly, alpha-haemolysin (Hla) targets and lyses rabbit red blood cells (RBC), releasing haemoglobin, a rich iron source utilized by S. aureus for growth (Pishchany et al., 2010; Torres et al., 2010).”
BackgroundSelf-citationZapotoczna, M., Jevnikar, Z., Miajlović, H., Kos, J., & Foster, T. J. (2012) · Cellular Microbiology · doi:10.1111/cmi.12097 · Cited by 82 · see citing works
“haemoglobin with similar affinities in the low nanomolar range (Dryla et al., 2007; Pishchany et al., 2010).”
BackgroundTaste for Blood: Hemoglobin as a Nutrient Source for Pathogens
Pishchany, G., & Skaar, E. P. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002535 · Cited by 73 · see citing works
“This is supported by the finding that variations within the amino acid sequence of hemoglobin derived from different mammals affect iron acquisition and virulence of the bacterial pathogen Staphylococcus aureus [28].”
BackgroundSelf-citationSoong, G., Martin, F. J., Chun, J., Cohen, T. S., Ahn, D. S., & Prince, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.295386 · Cited by 73 · see citing works
Geisinger, E., Chen, J. Y.-S., & Novick, R. P. (2012) · Journal of Bacteriology · doi:10.1128/jb.06685-11 · Cited by 70 · see citing works
Haemophore functions revisited
Wandersman, C., & Delepelaire, P. (2012) · Molecular Microbiology · doi:10.1111/j.1365-2958.2012.08136.x · Cited by 70 · see citing works
“In fact, ‘in vitro’ experiments have shown that S. aureus preferentially imports haem iron rather than transferrin iron (Skaar et al., 2004) and that human haemoglobin is the preferred haemoglobin source (Pishchany et al., 2010).”
BackgroundInfluentialBenson, M. A., Lilo, S., Wasserman, G. A., Thoendel, M., Smith, A. P., Horswill, A. R., Fraser, J. D., Novick, R. P., Shopsin, B., & Torres, V. J. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07720.x · Cited by 62 · see citing works
“abscesses in the kidney, heart and liver (Skaar et al., 2004; Torres et al., 2007; Corbin et al., 2008; Pishchany et al., 2010).”
BackgroundSelf-citationTseng, C. W., Biancotti, J. C., Berg, B. L., Gate, D., Kolar, S. L., Müller, S., Rodriguez, M., Rezai-Zadeh, K. P., Fan, X., Beenhouwer, D. O., et al. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005292 · Cited by 67 · see citing works
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“aureus compared with humans secondary to the microorganism’s preferential ability to take iron needed to proliferate from host hemoglobin in humans (33).”
BackgroundRegulation of host hemoglobin binding by the Staphylococcus aureus Clp proteolytic system
Farrand, A. J., Reniere, M. L., Ingmer, H., Frees, D., & Skaar, E. P. (2013) · Journal of Bacteriology · doi:10.1128/jb.00505-13 · Cited by 56 · see citing works
“Moreover, the IsdB-hemoglobin interaction is critical to staphylococcal pathogenesis in a murine model of infection (10, 42, 49).”
BackgroundSelf-citationComparative Genomics of the Staphylococcus intermedius Group of Animal Pathogens
Zakour, N. L. B., Beatson, S. A., van den Broek, A. H. M., et al. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00044 · Cited by 59 · see citing works
“Furthermore, there are known host-dependent differences in the availability of iron which influence the mechanisms of iron acquisition employed by staphylococci (Pishchany et al., 2010).”
Iron-Regulated Surface Determinant (Isd) Proteins of Staphylococcus lugdunensis
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“simulans and Corynebacterium diphtheriae, whereas environmental bacteria that infect numerous hosts, such as Acinetobacter baumannii, Pseudomonas aeruginosa, Bacillus anthracis, and Bacillus cereus, grow at comparable levels on hHb and mHb (55, 56).”
InfluentialStructural Basis for Hemoglobin Capture by Staphylococcus aureus Cell-surface Protein, IsdH
Kumar, K. K., Jacques, D. A., Pishchany, G., Caradoc-Davies, T. T., Spirig, T., Malmirchegini, G. R., Langley, D. B., Dickson, C. F., Mackay, J. P., Clubb, R., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.287300 · Cited by 58 · see citing works
Self-citationSpirig, T., Malmirchegini, G. R., Zhang, J., Robson, S. A., Sjodt, M., Liu, M., Kumar, K. K., Dickson, C. F., Gell, D. A., Lei, B., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.419119 · Cited by 57 · see citing works
Fingerprint Biometric System Hygiene and the Risk of COVID-19 Transmission
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“Pseudomonas aeruginosa[105],Enterobacteriaceae [105], HBV [28], HSV [26,51] Secretion from wounds and sores”
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Humanized Mouse Models of Staphylococcus aureus Infection
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Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models
Mrochen, D. M., de Oliveira, L. M. F., Raafat, D., & Holtfreter, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197061 · Cited by 53 · see citing works
“aureus binds hHb more efficiently than murine hemoglobin - Enhanced IsdB-mediated disease severity in hHb expressing mice - Increased susceptibility of hHb-expressing mice to systemic staphylococcal infection [153]”
BackgroundLi, Y., & Hu, B. (2012) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2012.07.006 · Cited by 52 · see citing works
Dickson, C. F., Kumar, K. K., Jacques, D. A., Malmirchegini, G. R., Spirig, T., Mackay, J. P., Clubb, R., Guss, J. M., & Gell, D. A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.545566 · Cited by 51 · see citing works
“aureus bacteremia in a mouse model (22), and deletion of IsdB protects against infections in heart (13, 23) and kidney (9, 24), indicating that Hb receptors have an important role in infection and that the Isd pathway might represent a therapeutic target for infections such as endocarditis, where S.”
BackgroundStudying Staphylococcal Leukocidins: A Challenging Endeavor
Tromp, A. T., & van Strijp, J. A. G. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00611 · Cited by 45 · see citing works
Mechanisms of host adaptation by bacterial pathogens
Barber, M. F., & Fitzgerald, J. R. (2024) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuae019 · Cited by 49 · see citing works
“For example, the hemoglobin receptor IsdB in S. aureus had pr e viousl y been shown to bind human hemoglobin mor e effectiv el y than mouse (Pishc han y et al. 2010 ).”
BackgroundYeung, Y. A., Foletti, D. L., Deng, X., Abdiche, Y. N., Strop, P., Glanville, J., Pitts, S. J., Lindquist, K. C., Sundar, P. D., Sirota, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13376 · Cited by 41 · see citing works
Lipopolysaccharide-induced hemolysis: Evidence for direct membrane interactions
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HowStaphylococcus aureusAdapts to Its Host
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The iron-regulated staphylococcal lipoproteins
Sheldon, J. R., & Heinrichs, D. E. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00041 · Cited by 43 · see citing works
“Moreover, growth impairment has been demonstrated for Isd mutants cultured on hemoglobin as a sole iron source (Torres et al., 2006; Pishchany et al., 2009, 2010); subsequent to hemoglobin binding at the cell surface and heme extraction, heme is likely never free from a protein and is shuttled…”
BackgroundStreptococcus pneumoniae Invades Erythrocytes and Utilizes Them to Evade Human Innate Immunity
Yamaguchi, M., Terao, Y., Mori-Yamaguchi, Y., Domon, H., Sakaue, Y., Yagi, T., Nishino, K., Yamaguchi, A., Nizet, V., & Kawabata, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077282 · Cited by 42 · see citing works
“The concentrations of these inhibitors were previously shown to prevent or minimize reactions [18,19,20,21,22].”
BackgroundMethodSortase A promotes virulence in experimental Staphylococcus lugdunensis endocarditis
Heilbronner, S., Hanses, F., Monk, I. R., Speziale, P., & Foster, T. J. (2013) · Microbiology · doi:10.1099/mic.0.070292-0 · Cited by 43 · see citing works
Immunomodulation and Disease Tolerance to Staphylococcus aureus
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“models of disease [2,9].”
Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence
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Self-citationvan Dijk, M. C., de Kruijff, R. M., & Hagedoorn, P.-L. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.857237 · Cited by 41 · see citing works
The impact of metal sequestration on Staphylococcus aureus metabolism
Hammer, N. D., & Skaar, E. P. (2011) · Current Opinion in Microbiology · doi:10.1016/j.mib.2011.11.004 · Cited by 40 · see citing works
“The absence of iron, manganese, or zinc severely impedes staphylococcal growth in vivo and in vitro [9,12].”
BackgroundSelf-citationStaphylococcus aureus: setting its sights on the human innate immune system
Buchan, K. D., Foster, S. J., & Renshaw, S. A. (2019) · Microbiology · doi:10.1099/mic.0.000759 · Cited by 33 · see citing works
Labile heme impairs hepatic microcirculation and promotes hepatic injury
Englert, F. A., Seidel, R. A., Galler, K., Gouveia, Z. L., Soares, M. P., Neugebauer, U., Clemens, M. G., Sponholz, C., Heinemann, S. H., Pohnert, G., et al. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108075 · Cited by 32 · see citing works
Direct Heme Uptake by Phytoplankton-Associated Roseobacter Bacteria
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“To circumvent this contamination, purified human hemoglobin was prepared in the Skaar laboratory at Vanderbilt University by anion exchange high-performance liquid chromatography and protein dialysis (54) and used in all subsequent experiments.”
MethodStaphylococcus aureus Growth using Human Hemoglobin as an Iron Source
Pishchany, G., Haley, K. P., & Skaar, E. P. (2013) · Journal of Visualized Experiments · doi:10.3791/50072 · Cited by 29 · see citing works
Self-citationStreit, B. R., Kant, R., Tokmina‐Lukaszewska, M., Celis, A. I., Machovina, M. M., Skaar, E. P., Bothner, B. B., & DuBois, J. L. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.666560 · Cited by 28 · see citing works
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“The results demonstrated that inflammasome activity was mediated by Hla in host cells, this outcome is in agreement with previous studies [25].”
ResultBennett, M. R., Bombardi, R. G., Kose, N., Parrish, E. H., Nagel, M. B., Petit, R. A., Read, T. D., Schey, K. L., Thomsen, I. P., Skaar, E. P., et al. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiy635 · Cited by 29 · see citing works
Self-citationHow Severe Anaemia Might Influence the Risk of Invasive Bacterial Infections in African Children
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Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia
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Jung, E., Perrone, E. E., Liang, Z., Breed, E. R., Dominguez, J. A., Clark, A. T., Fox, A. C., Dunne, W. M., Burd, E. M., Farris, A. B., et al. (2011) · Shock · doi:10.1097/shk.0b013e3182360faf · Cited by 28 · see citing works
“aureus compared with humans secondary to the microorganism’s preferential ability to take iron needed to proliferate from host hemoglobin in humans (36).”
BackgroundBrauckmann, S., Effenberger‐Neidnicht, K., Nagel, M., Mayer, C., Peters, J., & Hartmann, M. (2019) · Inflammation · doi:10.1007/s10753-019-01038-6 · Cited by 20 · see citing works
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“IsdB preferentially binds human hemoglobin (13); therefore, the Isd system is a logical target for intervention against S.”
BackgroundHeilbronner, S., Monk, I. R., Brozyna, J. R., Heinrichs, D. E., Skaar, E. P., Peschel, A., & Foster, T. J. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006246 · Cited by 24 · see citing works
“lugdunensis was shown to be human specific and not to tolerate mouse hb [10, 14].”
BackgroundSelf-citationBotelho-Nevers, É., Verhoeven, P. O., Paul, S., Grattard, F., Pozzetto, B., Berthelot, P., & Lucht, F. (2013) · Expert Review of Vaccines · doi:10.1586/14760584.2013.840091 · Cited by 27 · see citing works
An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis
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Biofilm Formation by Clinical Isolates and Its Relevance to Clinical Infections
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Targeting the host–pathogen interface for treatment of Staphylococcus aureus infection
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Energetics underlying hemin extraction from human hemoglobin by Staphylococcus aureus
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van den Berg, S., Koedijk, D. G. A. M., Back, J. W., Neef, J., Dreisbach, A., van Dijl, J. M., Bakker‐Woudenberg, I. A. J. M., & Buist, G. (2015) · PLoS ONE · doi:10.1371/journal.pone.0116847 · Cited by 24 · see citing works
“aureus infection process in humans due to various differences among which differences in host cell proteins such as hemoglobin [57] and the requirement for high bacterial inocula [58] in the non-human host.”
BackgroundAntivirulence Agents Against MRSA
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Dickson, C. F., Jacques, D. A., Clubb, R., Guss, J. M., & Gell, D. A. (2015) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s1399004715005817 · Cited by 22 · see citing works
“Two of the Isd proteins, IsdB and IsdH, are cell-surface proteins that bind to Hb and remove haem groups by a process that is not completely understood (Dryla et al., 2003, 2007; Torres et al., 2006; Pilpa et al., 2009; Pishchany et al., 2010; Krishna Kumar et al., 2011; Dickson et al., 2014).”
BackgroundPredictors of urinary tract infection in acute stroke patients
Li, Y., Xu, J., & Zhao, Y. (2020) · Medicine · doi:10.1097/md.0000000000020952 · Cited by 20 · see citing works
“The previous study has found that bacterial infections were associated with hemoglobin levels.([37]) Moreover, Eneroth’s research has found that patients with anemia were prone to infection,”
González, J. J. I., Hossain, M. F., Neef, J., Zwack, E. E., Tsai, C., Raafat, D., Fechtner, K., Herzog, L., Kohler, T. P., Schlüter, R., et al. (2023) · mBio · doi:10.1128/mbio.00225-23 · Cited by 17 · see citing works
“S. aureus mutants lacking IsdB are strongly attenuated when free iron is limited (25, 29, 30).”
BackgroundSelf-citationChan, C.-Y., Cheng, C., Shui, H., Ku, H., & Su, W. (2021) · Tzu Chi Medical Journal · doi:10.4103/tcmj.tcmj_58_21 · Cited by 21 · see citing works
“Furthermore, iron helps bacterial growth [42].”
Fernandez, J., Hilliard, J. J., Morrow, B. J., Melton, J. L., Flamm, R. K., Barron, A. M., & Lynch, A. S. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00471-11 · Cited by 18 · see citing works
“aureus to bind hemoglobin derived from humans compared to that derived from other mammals, including mice (28).”
BackgroundEllis‐Guardiola, K., Mahoney, B. J., & Clubb, R. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.607679 · Cited by 18 · see citing works
“In addition, Hb residues at this interface have rapidly changed during primate evolution, consistent with it being the focal point for repeated evolutionary conflicts in the battle for iron during host-pathogen interactions (Pishchany et al., 2010; Choby et al., 2018).”
BackgroundThe Role of Gram-Positive Surface Proteins in Bacterial Niche- and Host-Specialization
Pickering, A. C., & Fitzgerald, J. R. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.594737 · Cited by 18 · see citing works
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Molecular Basis for the Evolution of Species-Specific Hemoglobin Capture by Staphylococcus aureus
Choby, J. E., Buechi, H. B., Farrand, A. J., Skaar, E. P., & Barber, M. F. (2018) · mBio · doi:10.1128/mbio.01524-18 · Cited by 15 · see citing works
“Growth using hemoglobin as a sole iron source in both assays is IsdB dependent (11, 13, 22).”
Self-citationThe Pathogenicity Mechanisms of Staphylococcus aureus
Młynarczyk-Bonikowska, B., & Rudnicka, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262411803 · Cited by 21 · see citing works
“S. aureus is primarily a human pathogen, and the S. aureus hemoglobin receptor IsdB binds human hemoglobin more effectively than hemoglobin from other animal species [221].”
Chen, F., Zhao, Q., Yang, Z., Chen, R., Pan, H., Wang, Y., Liu, H., Cao, Q., Gan, J., Liu, X., et al. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012425 · Cited by 11 · see citing works
- Authors
- Pishchany, G., McCoy, A. L., Torres, V. J., Krause, J. C., Crowe, J. E., Fabry, M. E., & Skaar, E. P.
- Affiliations
- Vanderbilt University (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Skaar, Eric P.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 8
- Issue
- 6
- Pages
- 544-550
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3032424
- OpenAlex
- W2013138417
- Cited by
- 142
- References
- 32
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 11 · 2019: 8 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 15 · 2014: 8 · 2013: 15 · 2012: 19
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Staphylococcus aureus, human hemoglobin, ISDB, hemoglobin receptor, iron acquisition, host-pathogen interaction, bacterial virulence, mouse infection model
- MeSH terms
- Animals, Hemoglobins, Humans, Iron, Mice, Transgenic, Mutation
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