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Cited by 379Antimicrobial Resistance in StaphylococcusBacterial Genetics and BiotechnologyIron Metabolism and Disorders

Molecular Mechanisms of Staphylococcus aureus Iron Acquisition

Open access
Hammer, Neal D., Skaar, Eric P.·2011·Annual Review of Microbiology
DOI 10.1146/annurev-micro-090110-102851PMC PMC3807827
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Abstract

The unique redox potential of iron makes it an ideal cofactor in diverse biochemical reactions. Iron is therefore vital for the growth and proliferation of nearly all organisms, including pathogenic bacteria. Vertebrates sequester excess iron within proteins in order to alleviate toxicity and restrict the amount of free iron available for invading pathogens. Restricting the growth of infectious microorganisms by sequestering essential nutrients is referred to as nutritional immunity. In order to circumvent nutritional immunity, bacterial pathogens have evolved elegant systems that allow for the acquisition of iron during infection. The gram-positive extracellular pathogen Staphylococcus aureus is a commensal organism that can cause severe disease when it gains access to underlying tissues. Iron acquisition is required for S. aureus colonization and subsequent pathogenesis. Herein we review the strategies S. aureus employs to obtain iron through the production of siderophores and the consumption of host heme.

AI snapshot

Written from the paper’s full text.

TL;DR

This review describes how *Staphylococcus aureus* obtains iron during infection despite host nutritional immunity, focusing on siderophore-mediated iron theft and heme acquisition. It argues that these pathways are central to colonization and pathogenesis and are potential therapeutic targets.

Key findings

  • Host iron is mostly unavailable to extracellular pathogens: over 90% of mammalian iron is intracellular, and heme accounts for about 80% of host iron; *S. aureus* prefers heme-iron and can use hemoglobin, haptoglobin-hemoglobin, and intact erythrocytes as iron sources in vitro.
  • *S. aureus* produces two characterized siderophores, staphyloferrin A (479 Da) and staphyloferrin B (448 Da), which are Fur-regulated, synthesized via non-ribosomal peptide synthetase-independent pathways, and imported through HtsABC and SirABC, respectively; FhuC supplies ATPase activity for their transport.
  • The iron-regulated surface determinant (Isd) system mediates heme capture and passage through the cell wall: IsdA, IsdB, and IsdH are surface receptors, IsdC transfers heme through the wall, and IsdDEF is the membrane ABC transporter; IsdG and IsdI degrade heme to staphylobilin, with 64% amino acid identity and structures superimposable at 1.0 Å RMSD.
  • Heme toxicity is countered by HssRS-dependent up-regulation of HrtAB, reported as 45-fold after sub-lethal heme exposure; loss of HssR or HrtA produces hypervirulence in a murine abscess model, while IsdB inactivation reduces bacterial burden in spleen and kidneys and cardiac colonization by two orders of magnitude.

Methods

  • Narrative review synthesizing published genetic, biochemical, structural, and animal-model studies on *S. aureus* iron acquisition.
  • Covers host iron sequestration, Fur regulation, staphyloferrin A/B biosynthesis and transport, xenosiderophore uptake, Isd-mediated heme uptake and degradation, and heme toxicity responses.
  • No primary experimental sample or new dataset is reported; the paper is a literature synthesis rather than an original research study.

Limitations

  • The paper states that animal infection models are limited because bacterial virulence factors evolved to bind human-specific molecules; it notes that human hemoglobin differs from murine hemoglobin and that humanized mice were used to address this.
  • The paper identifies unresolved mechanistic questions, including the identity of the HrtAB substrate and detoxification mechanism, the ligand that activates HssS, the in vivo electron donor for IsdG/IsdI, and whether an additional membrane transporter imports heme-iron.
  • Evident from the text: as a review, it does not present new experimental data, and its conclusions depend on the cited studies and the state of the field at the time.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1146/annurev-micro-090110-102851

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 118 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    S. aureus produces two distinct siderophores, staphyloferrin A and staphyloferrin B.

    “S. aureus produces two distinct siderophores named staphyloferrin A and staphyloferrin B that share many properties (Fig. 1A).”
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    • cites [6] source

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  • Premisecitation

    Vertebrates sequester iron in proteins to reduce free iron available to invading pathogens, a process called nutritional immunity.

    “Vertebrates sequester excess iron within proteins in order to alleviate toxicity and restrict the amount of free iron available for invading pathogens.”
    • Also stated in: § Introduction · plain
      “This process of iron sequestration by the host, also referred to as nutritional immunity, inhibits the growth of invading microorganisms (9, 84).”
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  • Premisecitation

    S. aureus cannot use the hemopexin-heme complex as an iron source.

    “This interaction favors the host as S. aureus cannot use the hemopexin-heme complex as a source of iron (78).”
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  • Premisereasoning

    S. aureus secretes hemolysins that lyse erythrocytes, releasing hemoglobin.

    “In order to access this rich source of iron, S. aureus lyses erythrocytes through the secretion of hemolysins resulting in the liberation of hemoglobin.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Fur is the iron-dependent regulator that mediates the change in S. aureus protein expression during iron starvation.

    “This change in protein expression is mediated by the iron-dependent ferric uptake regulator (fur) (29, 80).”
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  • Classified as probably not a substantial claim. 2

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    Premisecitation

    Iron acquisition is necessary for Staphylococcus aureus colonization and for the pathogenesis that follows.

    “Iron acquisition is required for S. aureus colonization and subsequent pathogenesis.”
    • Also stated in: § Introduction · plain
      “Nutrient iron is required for S. aureus growth and persistence within abscesses and hence must be acquired during infection (13, 71, 80, 82).”
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    Premisecitation

    In vitro, siderophore-mediated iron acquisition is the main way S. aureus takes iron from transferrin, suggesting that S. aureus lacks a transferrin receptor for iron acquisition.

    “In vitro studies have demonstrated that siderophore-mediated iron acquisition is the dominant mechanism by which S. aureus steals iron from transferrin, suggesting that S. aureus does not produce a transferrin receptor involved in iron acquisition (58).”
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    • cites [58] Park RY, 2005, J. Microbiol.

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    Premisecitation

    When iron is present, Fur binds the fur box upstream of Fur-regulated genes; when iron is limiting, Fur leaves the DNA and relieves transcriptional repression.

    “In the presence of iron, Fur binds a consensus DNA sequence known as the fur box, found upstream of fur-regulated genes. When iron becomes limiting, Fur releases from the DNA, alleviating Fur-mediated transcriptional repression (5).”
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    Premisecitation

    S. aureus can bind the hemoglobin-haptoglobin complex and use it as an iron source.

    “Despite the strength of the hemoglobin-haptoglobin complex, S. aureus is capable of binding this complex and utilizing it as a source of iron (78).”
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    Premisecitation

    Heme contains 80% of host iron and is the preferred iron source for S. aureus.

    “Heme represents 80% of iron within the host and is the preferred iron source of S. aureus (71).”
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    Premisecitation

    The genes for biosynthesis and import of staphyloferrin A and staphyloferrin B are regulated by Fur and are maximally expressed when iron is limiting.

    “The genes involved in the biosynthesis and import of both staphyloferrin A and B are regulated by Fur and are therefore maximally expressed in iron-limiting environments (29, 45).”
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    • cites [45] Lindsay JA, 1994, Infect. Immun. source

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    Premisecitation

    In mice infected with S. aureus, Fur-regulated genes are expressed in heart and kidney abscesses, suggesting that the bacteria are iron-starved in those organs.

    “In vivo imaging of S. aureus infected mice has demonstrated that Fur-regulated genes are expressed in heart and kidneys abscesses, suggesting that staphylococci are starved for iron in these organs (60, 63).”
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    Premisecitation

    Erythrocytes are present within abscesses, giving S. aureus access to heme iron during tissue colonization.

    “Scanning electron microscopy has established that erythrocytes are present with abscesses, confirming that S. aureus has abundant access to this critical nutrient source during tissue colonization (13).”
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    Premisenone given

    Staphyloferrin B is an alpha-hydroxycarboxylate siderophore composed of Dap, Dae, and alpha-ketoglutaric acid with a molecular mass of 448 Da.

    “Staphyloferrin B is an alpha-hydroxycarboxylate siderophore composed of L-2,3-diaminopropionic acid (Dap), 1,2-diaminoethane (Dae), and α-ketoglutaric acid with a molecular mass of 448 Daltons.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    S. aureus can use hydroxymate-type xenosiderophores as an iron source, and this uptake depends on fhuCBG.

    “Despite the fact that S. aureus has not been demonstrated to produce hydroxymate-type siderophores, this organism has the capacity to utilize these siderophores as a source of iron.”
    • Also stated in: § Transport of siderophores across the staphylococcal membrane · plain
      “The uptake of xenosiderophores by S. aureus is also dependent upon fhuCBG (65).”
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    Premisecitation

    Staphyloferrin A has a mass of 479 Da and is made of one D-ornithine linking two citrate molecules through amide bonds.

    “Biochemical experiments revealed that staphyloferrin A has a mass of 479 Daltons and is composed of a molecule of D–ornithine that links together two molecules of citrate via amide bonds (41).”
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    Premisecitation

    Under iron limitation, S. aureus increases fermentative metabolism and produces lactate, which lowers the pH and reduces transferrin's affinity for iron.

    “Under iron-limiting conditions S. aureus increases fermentative metabolism, resulting in the production of lactate. Secretion of lactate lowers the pH of the microenvironment and the affinity of transferrin for iron (29).”
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    Premisecitation

    In fur mutants, cytolytic toxins are more abundant and immunomodulatory toxins are decreased relative to wild type; this altered exoprotein profile increases susceptibility to neutrophil killing and reduces virulence in a murine pneumonia model.

    “In fur mutants the cytolytic toxins are more abundantly expressed while immunomodulatory toxins are decreased compared to wild type cells. This altered exoprotein profile leads to an increase in susceptibility to neutrophil killing and consequently, reduced virulence in a murine pneumonia model of infection (79).”
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    Premisecitation

    Heme is transferred unidirectionally from IsdB NEAT domain 2 to the NEAT domains of IsdA or IsdC, and from the IsdA NEAT domain to the IsdC NEAT domain.

    “Heme is transferred unidirectionally from NEAT domain 2 of IsdB to the NEAT domains of either IsdA or IsdC. Heme is also transferred in a unidirectional manner from the NEAT domain of IsdA to the NEAT domain of IsdC (46).”
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    Premisecitation

    Sortase A covalently anchors proteins to the S. aureus cell wall.

    “Sortase A (SrtA) is a transpeptidase that covalently anchors proteins to the cell wall of S. aureus (48–50).”
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    Premisecitation

    When grown with both transferrin and heme or hemoglobin, S. aureus preferentially imports and uses heme-iron, suggesting that heme-iron is the preferred iron source during infection.

    “In fact, S. aureus preferentially imports and utilizes heme-iron when grown in the presence of both transferrin and heme or hemoglobin, suggesting that heme-iron is the preferred source of iron during infection (71, 78).”
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    Premisecitation

    NEAT domains are conserved 125-amino-acid stretches found in proteins that neighbor putative iron transporters.

    “NEAT domains are conserved stretches of 125 amino acids found within proteins that neighbor putative iron transporters (2).”
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    Premisecitation

    A consensus fur box lies upstream of each Isd operon, so all these genes are iron-regulated.

    “A consensus fur box is located upstream of each of these operons and therefore all of these genes are iron-regulated (49, 63).”
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    Premisereasoning

    Inactivation of isdDEF impairs but does not abolish S. aureus growth on heme as the sole iron source, implying that at least one additional membrane transporter imports heme-iron.

    “However, inactivation of isdDEF impairs, but does not abolish, S. aureus growth on heme as the sole iron source. This implies that an additional membrane transporter(s) imports heme-iron.”
    Quote in the paperSubstantial claim

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    Premisecitation

    IsdH contains three NEAT domains; NEAT domain 1 binds hemoglobin and haptoglobin, NEAT domain 2 binds hemoglobin with nanomolar affinity, and NEAT domain 3 weakly binds heme.

    “IsdH contains three NEAT domains (25). Structural analysis of the IsdH NEAT domains revealed that NEAT domain 1 binds both hemoglobin and haptoglobin. NEAT domain 2 binds hemoglobin with nanomolar affinities and NEAT domain 3 weakly binds heme.”
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    Premisecitation

    Inactivation of isdE together with htsA significantly reduces virulence, showing the importance of these transporters for S. aureus survival in the host.

    “Inactivation of isdE together with htsA leads to a significant reduction in virulence demonstrating the importance of these transporters to S. aureus survival in the host (47).”
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    Premisecitation

    Heme can transfer bidirectionally from IsdH NEAT domain 3 to IsdB NEAT domain 2 and unidirectionally to the NEAT domains of IsdA, IsdC, and IsdE.

    “Heme can be transferred in a bidirectional fashion from NEAT domain 3 of IsdH to NEAT domain 2 of IsdB, and in a unidirectional fashion to the NEAT domains of IsdA, IsdC, and IsdE (52, 86).”
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    • cites [86]

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    Premisecitation

    IsdG and IsdI share 64% amino acid identity, and their crystal structures superimpose with a root mean square deviation of 1.0 Å.

    “The amino acid sequences of IsdG and IsdI share 64% identity and the crystal structures of IsdG and IsdI can be superimposed with a root mean square deviation of 1.0 Å, underscoring the significant similarity between these proteins (85).”
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  • May combine two claims.

    Premisecitation

    Inactivation of htsB and htsC reduces S. aureus heme-iron import and decreases bacterial burden in the liver and kidneys of infected mice.

    “Inactivation of htsB and htsC reduces the ability of S. aureus to import heme-iron, which results in a decrease in bacterial burden in the liver and kidneys of mice infected with these mutants (71).”
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    • cites [71] source

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    Premisecitation

    The haptoglobin-hemoglobin complex is a viable iron source for S. aureus and is bound by IsdH.

    “The haptoglobin-hemoglobin complex is also a viable source of iron for S. aureus and this complex is bound by IsdH (25, 27, 78) (Fig 1. B).”
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    Premisecitation

    In vitro, heme transfer through IsdA, IsdB, or IsdC to IsdE was confirmed by MCD and ESI-MS; the IsdC NEAT domain transfers heme to IsdE, but IsdA does not transfer heme to IsdE.

    “Transfer of heme through the cell wall-localized Isd proteins IsdA, IsdB, or IsdC to the membrane-localized heme receptor IsdE was confirmed in vitro using magnetic circular dichroism (MCD) and electrospray ionization mass spectrometry (ESI-MS). The NEAT domain of IsdC can transfer heme to IsdE. Heme is not transferred between IsdA and IsdE (52).”
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    Interpretationreasoning

    Using imported heme intact lowers the need for endogenous heme synthesis and reduces metabolic burden.

    “This reduces the requirement for endogenous heme synthesis and in effect decreases the metabolic burden on the bacterium.”
    Quote in the paperSubstantial claim

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    Premisereasoning

    Heme is a redox-active molecule that can be toxic at high levels.

    “However, this redox active molecule can also be toxic at high levels.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Inactivation of both isdG and isdI attenuates S. aureus in a murine systemic infection, which suggests that heme degradation and staphylobilin formation contribute to pathogenesis.

    “isdGI mutants are attenuated in the murine model of systemic infection implicating heme degradation and staphylobilin formation as being important for pathogenesis (63).”
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    Premisecitation

    The hrtAB system consists of the hrtA ATPase and hrtB permease in a bicistronic operon, and both are needed for adaptation to heme-mediated toxicity.

    “The ATPase of this system (hrtA) is encoded in a bicistronic operon with the predicted permease (hrtB), and both are required for adaptation to heme-mediated toxicity.”
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    • cites [73] source

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    Premisecitation

    IsdG protein stability requires heme; IsdG is degraded when heme is absent, whereas IsdI is not.

    “IsdG stability is also dependent on the presence of heme such that IsdG is degraded in the absence of heme while IsdI is not (63).”
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    Premisecitation

    Expression of HrtB without HrtA reduces membrane integrity and changes the protein secretion profile.

    “HrtB expression in the absence of HrtA results in a decrease in the integrity of the membrane and an altered protein secretion profile (4).”
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    Premisecitation

    Under iron-replete conditions, S. aureus imports substantial heme, does not express isdG or isdI, and distributes heme intact to the bacterial membrane.

    “Despite the fact that the primary function of heme uptake systems is to satisfy the nutrient iron need of S. aureus, appreciable heme is brought into the cell during iron replete conditions. In this case, isdG and isdI are not expressed and heme is instead distributed intact to the bacterial membrane (71).”
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    Interpretationreasoning

    IsdG-family enzymes are required during colonization and are absent from humans, making them potential clinical targets.

    “Targeting IsdG-family enzymes has significant clinical potential due to the requirement for these enzymes during colonization and the absence of this enzyme family within humans.”
    Quote in the paperSubstantial claim

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    Premisecitation

    hrtAB expression depends on HssRS, and loss of either hssS or hssR prevents adaptation to heme toxicity.

    “Expression of hrtAB is dependent on HssRS and inactivation of either hssS or hssR results in an inability to adapt to heme toxicity.”
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    Premisecitation

    Heme exposure activates HssS, causing autophosphorylation.

    “Heme exposure activates the histidine kinase, HssS, resulting in autophosphorylation.”
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  • May combine two claims.

    Interpretationreasoning

    In HssRS, heme toxicity is the environmental cue and hrtAB up-regulation is the physiological response.

    “In the case of HssRS, the environmental cue is heme toxicity and the physiological response is the up-regulation of hrtAB.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The Isd system plays a major role in S. aureus pathogenesis because iron is required during infection.

    “Considering the requirement for iron during infection, the Isd system plays a major role during pathogenesis.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Phosphorylated HssR binds a direct repeat in the hrtAB promoter and induces hrtAB transcription.

    “Phosphorylated HssR binds to a direct repeat sequence within the hrtAB promoter in order to induce transcription of hrtAB (74) (Fig. 2).”
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  • May combine two claims.

    Premisecitation

    In vitro, the NEAT domains of IsdH and IsdB can bind heme and transfer it directly to IsdC or IsdE.

    “in vitro data have demonstrated the NEAT domains of IsdH and IsdB can bind heme and transfer it directly to IsdC or IsdE (52).”
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  • May combine two claims.

    Interpretationreasoning

    IsdB is a potential vaccine candidate because it is important for infection and surface exposed.

    “The importance of IsdB to S. aureus infection combined with the surface exposed localization of the protein establishes IsdB as a potential vaccine candidate.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: IsdB is surface exposed.

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    Interpretationcitation

    IsdA is important for colonization and persistence in human skin and murine kidneys.

    “These results suggest that IsdA is important for the colonization and persistence of S. aureus in these two host environments.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Inactivation of isdH alone does not affect bacterial burden in this model, implicating IsdB as the critical hemoprotein receptor during systemic infection.

    “Inactivation of isdH alone does not affect bacterial burden in this model implicating IsdB as the critical hemoprotein receptor during systemic infection.”
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  • May combine two claims.

    Interpretationnone given

    S. aureus strains lacking individual Isd components cannot meet their iron need and are attenuated for growth in vertebrates.

    “S. aureus strains inactivated for individual components of the Isd system are unable to satisfy their nutrient iron need and are therefore attenuated for growth within vertebrates.”
    Quote in the paperSubstantial claim

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    Premisecitation

    In a murine abscess model, hssR or hrtA mutants show more overt infection symptoms and more liver abscesses than wild-type-infected mice.

    “In a murine abscess model of infection hssR or hrtA mutants exhibit more overt symptoms of infection and the number of abscesses in the liver is elevated compared to mice infected with wild type S. aureus (81).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] source

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    Premisecitation

    Antibodies against IsdA and IsdB rescue animals from lethal staphylococcal challenge and inhibit abscess formation.

    “Moreover, antibodies against IsdA and IsdB rescue animals from lethal staphylococcal challenge and inhibit abscess formation (39).”
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    Premisecitation

    This increased immunomodulatory protein expression impairs neutrophil migration and activation, promoting bacterial survival.

    “This results in an impairment in neutrophil migration and activation which promotes bacterial survival.”
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    • cites [98]

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    Premisecitation

    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.”
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    Interpretationreasoning

    IsdI and IsdG are independently required for full virulence, suggesting they have distinct roles during vertebrate colonization.

    “The finding that both IsdI and IsdG are independently required for full virulence suggests that these enzymes have distinct roles during vertebrate colonization.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The hypervirulence of ΔhrtA is specific to the liver and results from increased expression of immunomodulatory proteins.

    “The hypervirulence of ΔhrtA is specific to the liver and is due to increased expression of immunomodulatory proteins in these mutant strains [98].”
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  • May combine two claims.

    Interpretationreasoning

    S. aureus grown in iron-replete conditions transports exogenous heme intact to the membrane, implying it has alternative uses for heme.

    “The finding that S. aureus grown in iron-replete conditions transports exogenous heme to the membrane intact implies that S. aureus has alternative uses for heme.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    S. aureus siderophores take iron from host proteins, while the Isd system consumes host heme and releases iron.

    “S. aureus siderophores steal iron from host proteins while the Isd system consumes host heme and releases iron.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Colonization is reduced but not eliminated when either iron acquisition pathway is inactivated, suggesting both siderophore-iron and heme-iron are critical to pathogenesis.

    “Colonization is decreased but not abolished when either pathway is inactivated, suggesting that both siderophore-iron and heme-iron are critical to pathogenesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Both siderophore and heme-iron acquisition pathways are expressed in the iron-limited host environment.

    “Both pathways are expressed within the iron-limited host environment.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Both siderophore and heme-iron acquisition pathways are expressed in the iron-limited host environment.
54 of 54

  • The paper relies on this without support.

    Findings from in vitro assays and murine infection models are informative about S. aureus iron acquisition and pathogenesis in humans.

    “Animal models have confirmed that disrupting host iron homeostasis increases the severity of S. aureus infections (31).”
    “This altered exoprotein profile leads to an increase in susceptibility to neutrophil killing and consequently, reduced virulence in a murine pneumonia model of infection (79).”

  • The paper relies on this without support.

    Some Gram-positive pathogens rely entirely on heme scavenging for their respiratory pathways.

    “Consistent with this model, the respiratory pathways of some Gram positive pathogens rely entirely on the ability of the bacteria to scavenge heme.”

  • The paper relies on this without support.

    IsdB is surface exposed.

    “The importance of IsdB to S. aureus infection combined with the surface exposed localization of the protein establishes IsdB as a potential vaccine candidate.”

  • The paper relies on this without support.

    Human and murine hemoglobin differ considerably in surface-exposed amino acids.

    “There is a considerable amount of divergence between the surface exposed amino acids of human and murine hemoglobin.”

  • The paper relies on this without support.

    Nutritional immunity protects the host by sequestering iron and other essential nutrients.

    “Nutritional immunity protects the host from invading microorganisms by sequestering iron and other essential nutrients.”

  • The paper relies on this without support.

    Both siderophore and heme-iron acquisition pathways are expressed in the iron-limited host environment.

    “Both pathways are expressed within the iron-limited host environment.”
6 of 6

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Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Sortase B recognition motif is given in two different orders

    Minor

    The text identifies NPTQN as the motif recognized by Sortase B, but then identifies NPQTN as the motif on IsdC that Sortase B anchors. The two sequences differ in the order of their last three residues.

1 of 1

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References 86 · Cited by 379

Research works printed but not linked: 3

  1. Centers for Disease Control and Prevention. 2007. HIV/AIDS surveillance report. Vol. 17. Revised Edition
  2. Gladstone GP, 1971, Br. J. Exp. Pathol., 52, 452
  3. Park RY, 2005, J. Microbiol., 43, 183

Authors
Hammer, N. D., & Skaar, E. P.
Affiliations
Vanderbilt University (US)
ORCID
Venue
Annual Review of Microbiology
Publisher
Annual Reviews
Published
2011-10-13
Volume
65
Issue
1
Pages
129-147
ISSN
  • 0066-4227 (ISSN-L)
  • 1545-3251
DOI
10.1146/annurev-micro-090110-102851
PMC
PMC3807827
OpenAlex
W2124064813
Cited by
379
References
86
Citations by year
2026: 25 · 2025: 32 · 2024: 30 · 2023: 17 · 2022: 31 · 2021: 24 · 2020: 26 · 2019: 27 · 2018: 26 · 2017: 22 · 2016: 31 · 2015: 22 · 2014: 23 · 2013: 18 · 2012: 22
FWCI
1.62
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Microbiology (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, AI 057157, F32AI091244, F32-AI091244-01, AI0169233, R01AI069233, U54AI057157, R01AI073843)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
Staphylococcus aureus, iron acquisition, siderophores, heme acquisition, nutritional immunity, bacterial pathogenesis, bacterial colonization, iron metabolism
MeSH terms
Animals, Bacterial Proteins, Humans, Iron, Staphylococcal Infections, Staphylococcus aureus, Gene Expression Regulation, Bacterial, Siderophores

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