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Cited by 449Bacterial Genetics and BiotechnologyEscherichia coli research studiesTrace Elements in Health

Transition Metals and Virulence in Bacteria

Open access
Palmer, Lauren D., Skaar, Eric P.·2016·Annual Review of Genetics
DOI 10.1146/annurev-genet-120215-035146PMC PMC5125913
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Abstract

Transition metals are required trace elements for all forms of life. Due to their unique inorganic and redox properties, transition metals serve as cofactors for enzymes and other proteins. In bacterial pathogenesis, the vertebrate host represents a rich source of nutrient metals, and bacteria have evolved diverse metal acquisition strategies. Host metal homeostasis changes dramatically in response to bacterial infections, including production of metal sequestering proteins and the bombardment of bacteria with toxic levels of metals. In response, bacteria have evolved systems to subvert metal sequestration and toxicity. The coevolution of hosts and their bacterial pathogens in the battle for metals has uncovered emerging paradigms in social microbiology, rapid evolution, host specificity, and metal homeostasis across domains. This review focuses on recent advances and open questions in our understanding of the complex role of transition metals at the host-pathogen interface.

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Crossref · 10.1146/annurev-genet-120215-035146

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Claims the paper makes

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  • Interpretationcitation

    Siderophore-mediated acquisition of noniron metals is important in bacterial pathogenesis.

    “This pivotal finding established the importance of siderophore noniron metal acquisition in bacterial pathogenesis.”
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  • Premisecitation

    P. aeruginosa lineages colonized in cystic fibrosis patients evolved to prefer heme over the siderophore pyoverdine as an iron source.

    “Additionally, P. aeruginosa lineages colonized in cystic fibrosis patients evolved to prefer heme over the siderophore pyoverdine as an iron source (85).”
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  • Premisenone given

    In donors with high urine pH, lipocalin 2 complexes with catechols and Fe3+ to sequester iron from invading pathogens.

    “In donors with high urine pH, lipocalin 2 complexes with catechols and Fe3+ to sequester iron from invading pathogens.”
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  • Premisecitation

    Bacteria evolved stealth siderophores, including salmochelin and petrobactin, that evade lipocalin 2 binding.

    “In response, bacteria evolved to elaborate stealth siderophores that evade lipocalin 2 binding, including the highly glycosylated salmochelin produced by pathogenic enterobacteria and petrobactin produced by B. anthracis (1, 43).”
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  • Interpretationreasoning

    The intensity of competition in the host environment can drive bacterial populations to extinction.

    “The P. aeruginosa findings suggest that the intensity of competition in the host environment can drive bacterial populations to extinction.”
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    Premisecitation

    Calprotectin is an abundant neutrophil protein that chelates Zn2+ and Mn2+ and efficiently competes away these nutrient metals from numerous bacterial pathogens in vitro.

    “Calprotectin is an abundant neutrophil protein that can chelate Zn2+ and Mn2+ and efficiently competes away these nutrient metals from numerous bacterial pathogens in vitro (32).”
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    Premisecitation

    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).”
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    In Yersinia pseudotuberculosis, a type VI secretion system imports zinc by transporting a zinc-binding protein effector bound to zinc, and maximal virulence requires both the Znu and T6SS systems.

    “In Yersinia pseudotuberculosis, a type VI secretion system (T6SS) imports zinc by transporting a zinc-binding protein effector bound to zinc, and maximal virulence requires both the Znu and T6SS systems, thus expanding known roles for T6SS (139).”
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    Premisecitation

    Enterobactin binds Fe3+ more tightly than transferrin, allowing it to outcompete transferrin chelation.

    “For example, enterobactin produced by Enterobacteriaceae binds Fe3+ (Kd 10−51–10−49 M) more tightly than transferrin (Kd 10−24–10−20 M), thus outcompeting transferrin chelation (23, 81).”
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    Premisecitation

    In the lung, enterobactin is not required for Klebsiella pneumoniae pneumonia but is required for invasion into surrounding tissue, and its high Fe3+ affinity enables iron acquisition from transferrin in the perivascular space.

    “In the lung, enterobactin is not required for Klebsiella pneumoniae pneumonia but is required for invasion into surrounding tissue; its higher Fe3+ binding affinity enables K. pneumoniae to acquire iron from transferrin in the perivascular space (9).”
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    Premisecitation

    Lipocalin 2 is produced during the innate immune response to bacterial infection and sequesters siderophores such as enterobactin and bacillibactin.

    “The vertebrate host produces the siderophore-binding protein lipocalin 2, also known as siderocalin or neutrophil gelatinase–associated lipocalin, during the innate immune response to bacterial infection to sequester siderophores such as enterobactin or bacillibactin (1, 44).”
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    Premisecitation

    S. aureus liver abscesses are severely depleted of zinc and manganese, and this depletion depends on S100A8/S100A9 heterodimers.

    “Molecular imaging by mass spectrometry demonstrated that Staphylococcus aureus liver abscesses are severely depleted of zinc and manganese and depletion depends on heterodimers of S100A8/S100A9 (calprotectin) (30).”
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    Premisecitation

    Experimental evolution in Pseudomonas aeruginosa showed that relatedness and low competition select for cooperation, whereas local competition selects for cheaters.

    “Experimental evolution in P. aeruginosa showed that relatedness and low competition selects for cooperation (i.e., siderophore production), whereas local competition selects for cheaters (53).”
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    Premisecitation

    Transferrin inhibits microbial growth by iron chelation in egg whites and human plasma, and lactoferrin has similar activity at mucosal surfaces.

    “The protein transferrin was first reported to inhibit microbial growth by iron chelation in egg whites and human plasma in the 1940s, and lactoferrin was later shown to have similar properties at mucosal surfaces (105, 120, 121)”
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    Premisecitation

    Obligate human pathogens of Neisseria spp. are host restricted based on their transferrin-binding proteins, a fact exploited to develop murine meningitis models by introducing or expressing human transferrin.

    “The obligate human pathogens of Neisseria spp. are host restricted based on their transferrin-binding proteins, a fact that has been exploited to develop murine models for meningitis by introducing or expressing human transferrin (102, 148).”
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    Interpretationnone given

    Host metal homeostasis changes during bacterial infection, including production of metal-sequestering proteins and exposure of bacteria to toxic metal levels.

    “Host metal homeostasis changes dramatically in response to bacterial infections, including production of metal sequestering proteins and the bombardment of bacteria with toxic levels of metals.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Long-term P. aeruginosa infection in the cystic fibrosis lung selects for siderophore cheating, eventually driving some populations to lose siderophore production and reducing fitness in the iron-limited host.

    “Importantly, long-term P. aeruginosa infection in the cystic fibrosis lung was recently shown to select for siderophore cheating, eventually driving some populations to lose siderophore production and thus reduce fitness in the iron-limited host (7).”
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    Premisecitation

    S100A12 binds both Zn2+ and Cu2+, is induced in H. pylori infection, and limits bacterial growth through zinc chelation.

    “Similarly, S100A12 (calgranulin C), which binds both Zn2+ and Cu2+, is induced in H. pylori infection and limits bacterial growth through zinc chelation (56).”
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    Premisecitation

    During Salmonella enterica gastrointestinal infection, salmochelin provides a competitive advantage over commensals, but the probiotic E. coli strain Nissle outcompetes S. enterica for siderophores and reduces its colonization.

    “During S. enterica gastrointestinal infection, S. enterica uses salmochelin to gain a competitive advantage over commensals but is outcompeted for siderophores by the probiotic E. coli strain Nissle, which reduces S. enterica colonization (33, 113).”
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    Interpretationreasoning

    Bacteria have evolved systems to evade host metal sequestration and to resist metal toxicity.

    “Presumably, in response, bacteria have evolved systems to subvert metal sequestration and toxicity.”
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    Premisecitation

    Heme acquisition is required for virulence in Staphylococcus aureus, Bacillus anthracis, and Streptococcus pyogenes.

    “Heme acquisition is required for virulence in Staphylococcus aureus, B. anthracis, and Streptococcus pyogenes (27).”
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    Premisecitation

    In Yersinia pestis, yersiniabactin binds zinc and is transported into the cell by the dedicated Zn2+-yersiniabactin importer YbtX; in septicemic plague, virulence defect occurs only in strains lacking both the znu transporter and yersiniabactin biosynthesis genes.

    “In Y. pestis, Bobrov et al. (16) demonstrated that the siderophore yersiniabactin binds zinc and is transported into the cell using a dedicated Zn2+-yersiniabactin importer, YbtX. Importantly, in a model of septicemic plague, Y. pestis displays a virulence defect only in strains lacking both the znu transporter and yersiniabactin biosynthesis genes.”
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    In Y. pestis, mutants lacking both manganese transport systems display no defect in pneumonic plague but are attenuated in bubonic plague.

    “In Y. pestis, mutants lacking both transport systems display no defect in pneumonic plague but are attenuated in bubonic plague (108).”
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    In Borrelia burgdorferi, the BmtA manganese transporter is required for virulence and is related to eukaryotic ZIP family transporters rather than bacterial manganese importers.

    “In the Lyme disease pathogen B. burgdorferi, the BmtA manganese transporter is required for virulence. Curiously, BmtA is not related to bacterial manganese importers but, rather, to the ZIP (Zrt/Irt-like protein) family transporters in eukaryotes (106).”
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    Premisecitation

    Transcriptional profiling of M. tuberculosis in human macrophages identified signs of metal intoxication in bacteria and in the host, revealing a burst of free zinc in macrophages and intraphagosomal zinc accumulation.

    “Transcriptional profiling of M. tuberculosis in human macrophages identified signs of metal intoxication in bacteria and in the host, revealing a burst of free zinc in macrophages and intraphagosomal zinc accumulation (18).”
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    Premisecitation

    Calprotectin enhances S. enterica growth in the inflamed gut, presumably because S. enterica can outcompete the gut microbiota for limited zinc.

    “Calprotectin enhances S. enterica growth in the inflamed gut, presumably because S. enterica can outcompete the gut microbiota for limited zinc (79).”
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    Premisecitation

    In S. aureus, the nickel transporter Nik is required for urease activity and efficient kidney colonization, and the cobalt and nickel transporter Cnt is additionally required for infection in systemic and urinary tract infections in mice.

    “In S. aureus, the nickel transporter Nik is required for urease activity and efficient kidney colonization, and the cobalt and nickel transporter Cnt is additionally required for infection in systemic and urinary tract infections in mice (63, 114).”
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    For S. aureus, mutants lacking MntH and ABC transport systems have a lower burden in the liver during systemic infection but maintain their burden in the kidney.

    “For S. aureus, mutants lacking MntH and ABC transport systems have a lower burden in the liver during systemic infection but maintain their burden in the kidney (73).”
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    Human nramp1 polymorphisms affect susceptibility to tuberculosis, meningococcal diseases, and leprosy.

    “Human nramp1 polymorphisms affect susceptibility to tuberculosis, meningococcal diseases, and leprosy (14).”
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    Premisecitation

    During bacterial infection, interferon-γ induces expression of copper transport protein 1 (CTR1) to import copper from the environment to ATOX1, which then shuttles copper to the ATP7A transporter at the phagolysosome membrane for copper accumulation.

    “During bacterial infection, interferon-γ induces expression of copper transport protein 1 (CTR1) to import copper from the environment to ATOX1, which then shuttles copper to the ATP7A transporter at the membrane of the phagolysosome for copper accumulation (74, 143, 145)”
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    Copper acquisition by the fungal pathogen Cryptococcus neoformans is critical for meningoencephalitis virulence but not pneumonia, demonstrating that some host niches are copper limited.

    “Copper acquisition by the fungal pathogen Cryptococcus neoformans is critical for meningoencephalitis virulence but not pneumonia, demonstrating that some host niches are copper limited (129).”
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    Premisecitation

    During S. enterica infection of the gut, manganese acquisition is required for infection, and manganese restriction is IL-22 dependent but calprotectin-independent.

    “During S. enterica infection of the gut, manganese acquisition is required for infection, where manganese restriction is IL-22 dependent but calprotectin-independent (35).”
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    The commonly used laboratory mouse strains C57BL/6 and BALB/c are Nramp1-deficient and rapidly succumb to S. enterica infection, in contrast to Nramp1-sufficient mouse strains.

    “The commonly used laboratory mouse strains C57BL/6 and BALB/c are Nramp1-deficient and rapidly succumb to S. enterica infection, in contrast to Nramp1-sufficient mouse strains (135).”
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    • cites [135] Vidal SM, 1996, J. Immunol. source

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    Premisecitation

    The primary targets of copper toxicity in E. coli and N. gonorrhoeae are iron-sulfur cluster proteins in branched chain amino acid and heme biosynthesis, respectively; in S. pneumoniae, the primary target is the manganese-containing aerobic ribonucleotide reductase.

    “The primary targets of its toxicity in E. coli and N. gonorrhoeae are iron-sulfur cluster proteins in branched chain amino acid and heme biosynthesis, respectively; in S. pneumoniae, the primary target is the manganese-containing aerobic ribonucleotide reductase (38, 68, 83)”
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    Characterization of staphylopine marks the first description of a nicotianamine-like molecule in bacteria and the first broad-spectrum metallophore.

    “Characterization of staphylopine marks the first description of a nicotianamine-like molecule in bacteria and the first broad-spectrum metallophore.”
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    Premisecitation

    Nickel is an essential cofactor for virulence factors including nickel-iron hydrogenase and urease in H. pylori, where the NixA nickel transporter is required for virulence.

    “Nickel is well established as an essential cofactor for virulence factors, including nickel-iron hydrogenase and urease in H. pylori, where the NixA nickel transporter is required for virulence (41, 100).”
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    Premisecitation

    Uropathogenic E. coli use Cu2+-yersiniabactin to protect against copper toxicity and oxidative stress through at least two mechanisms: binding prevents catechol-mediated Cu2+ reduction to Cu+, and Cu2+-yersiniabactin exhibits extracellular and catalytic superoxide dismutase-like activity.

    “Uropathogenic E. coli use Cu2+-yersiniabactin to protect against copper toxicity and oxidative stress through at least two mechanisms: (a) binding to yersiniabactin prevents catechol-mediated Cu2+ reduction to Cu+, which could participate in Fenton chemistry, and (b) Cu2+-yersiniabactin exhibits extracellular and catalytic superoxide dismutase–like activity (25, 26).”
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    Premisecitation

    Zinc intoxication competitively inhibits manganese binding to an importer in S. pneumoniae and the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase in S. pyogenes.

    “Zinc intoxication competitively inhibits manganese binding to an importer in S. pneumoniae and the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase in S. pyogenes (88, 104)”
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    Premisecitation

    Yersiniabactin binds Cu2+ in physiologically relevant environments, and Cu2+-yersiniabactin can be imported in uropathogenic E. coli using the TonB-dependent siderophore importer FyuA.

    “Mounting evidence demonstrates that the siderophore yersiniabactin binds Cu2+ in physiologically relevant environments and that Cu2+-yersiniabactin can be imported in uropathogenic E. coli using the TonB-dependent siderophore importer FyuA (26, 75).”
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    Premisecitation

    In patients with β-thalassemia, infectious disease is the second most common cause of death, with more than 50% caused by Enterobacteriaceae.

    “In patients with β-thalassemia, which is caused by mutations in the hemoglobin β-chain, infectious disease is the second most common cause of death (>50% caused by Enterobacteriaceae) (138).”
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    Premisecitation

    About one-third of the world's population has zinc deficiency.

    “Approximately one-third of the world's population suffers from zinc deficiency, which is associated with increased rates of diarrhea and pneumonia (111).”
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    • Rests on an assumption: Links between infection and dietary deficiencies of iron, copper, and zinc are well established.

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    Premisecitation

    MntX appears to be important for maintaining the appropriate manganese/iron ratio, which is particularly important in low-iron environments.

    “MntX appears to be important for maintaining the appropriate manganese/iron ratio, which is particularly important in low-iron environments (134).”
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    Premisecitation

    An increase in cytosolic zinc due to the transporter ZIP8 is an innate immune signaling mechanism in macrophages and lung epithelial cells; zinc accumulation modulates NF-κB activation and inflammation.

    “Interestingly, an increase in cytosolic zinc due to the transporter ZIP8 is an innate immune signaling mechanism in macrophages and lung epithelial cells. Specifically, zinc accumulation modulates nuclear factor (NF)-κB activation and inflammation (80).”
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    Premisecitation

    In a Mongolian gerbil model of stomach colonization, H. pylori requires resistance to the cadmium, zinc, and nickel (Czn) exporter, suggesting that H. pylori encounters metal stress in the host.

    “In a Mongolian gerbil model of stomach colonization, H. pylori requires resistance to the cadmium, zinc, and nickel (Czn) exporter, suggesting that H. pylori encounters metal stress in the host (125).”
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    Premisecitation

    Resistance to manganese toxicity by the manganese exporter MntX is conserved in N. meningitidis but not N. gonorrhoeae, suggesting that manganese homeostasis differs in their infectious niches.

    “For example, resistance to manganese toxicity by the manganese exporter MntX is conserved in N. meningitidis but not N. gonorrhoeae, suggesting that manganese homeostasis differs in their infectious niches (134).”
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    Premisecitation

    The hereditary blood disorders β-thalassemia and hemochromatosis can cause iron overload and are associated with increased rates of infection.

    “The hereditary blood disorders β-thalassemia and hemochromatosis can cause iron overload and are associated with increased rates of infection (141).”
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    Premisecitation

    S. pyogenes requires MntE for virulence and resistance to manganese toxicity and hydrogen peroxide stress, apparently due to dysregulation of metal homeostasis.

    “S. pyogenes also requires MntE for virulence and resistance to manganese toxicity and hydrogen peroxide stress, apparently due to dysregulation of metal homeostasis (132).”
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    Interpretationreasoning

    Bacterial siderophores, as secreted public goods, are a promising therapeutic target with lower selective pressure for resistance because a resistant bacterium does not necessarily benefit.

    “As secreted public goods, bacterial siderophores present a promising therapeutic target with reduced selective pressure for resistance, because the bacterium that evolves resistance does not necessarily benefit.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Vaccines against bacterial siderophores could decouple resistance and selective pressure without causing metal intoxication of the host.

    “For example, vaccines against bacterial siderophores could similarly decouple resistance and selective pressure without causing metal intoxication of the host.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A low molecular weight thiol, bacillithiol, is the labile zinc buffer in Bacillus subtilis.

    “Recent work defining a low molecular weight thiol as the labile zinc buffer in Bacillus subtilis has expanded our understanding of metal homeostasis in bacteria, but the role of metal buffering and metallochaperones in pathogenesis remains largely unexplored (82).”
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    Premisecitation

    Respiratory syncytial virus infection causes transferrin release, increasing available iron and promoting Pseudomonas aeruginosa infection and biofilm formation.

    “Infection by respiratory syncytial virus causes transferrin release, increasing available iron and promoting P. aeruginosa infection and biofilm formation (61).”
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    • Rests on an assumption: Mixed infections can change the host's metal environment.
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  • The paper relies on this without support.

    Hemochromatosis is linked to more infections by several pathogens that are normally noninvasive.

    “Hemochromatosis is also associated with increased infection by multiple, normally noninvasive pathogens.”

  • The paper relies on this without support.

    Iron overload can result from dietary excess, often from inappropriate iron supplementation.

    “Excess iron can be induced by dietary iron overload, generally due to inappropriate iron supplementation.”

  • The paper relies on this without support.

    Links between infection and dietary deficiencies of iron, copper, and zinc are well established.

    “There are well-established links between infection and dietary deficiencies of iron, copper, and zinc.”

  • The paper relies on this without support.

    Copper and zinc support immune development and can act as bacterial toxins, and intracellular zinc acts as an immune signal.

    “Copper and zinc are important for immune development and can serve as bacterial intoxicants, and intracellular zinc levels serve as an immune signal.”

  • The paper relies on this without support.

    Zinc is essential for immune function.

    “Because zinc is critical for immune function, the role of enhanced bacterial virulence in a zinc-deficient host is unclear.”

  • The paper relies on this without support.

    Mixed infections can change the host's metal environment.

    “Additionally, polymicrobial infections can modulate the metal environment in the host.”

  • The paper relies on this without support.

    Iron deficiency is specifically linked to Helicobacter pylori infection.

    “Iron deficiency is specifically associated with H. pylori infection, which is a leading cause of gastric cancer.”
7 of 7

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?

  • Iron and heme uptake proteins are associated with the virulence and pathogenicity of bacteria.

    “Some studies have reported that iron and heme uptake proteins are associated with the virulence and pathogenicity of bacteria (Palmer and Skaar, 2016) such as Streptococcus pneumonia (Brown et al., 2001), Staphylococcus aureus (Skaar et al., 2004), Vibrio cholera (Mey et al., 2005), enterotoxigenic Escherichia coli (Haines et al., 2015), and Pseudomonas aeruginosa (Minandri et al., 2016).”

    From The Heme Transporter HtsABC of Group A Streptococcus Contributes to Virulence and Innate Immune Evasion in Murine Skin Infections (2018) · cites this paper as Palmer and Skaar, 2016

  • Competition for limited iron became a conserved host defense against infection in plants and animals and also a microbial virulence factor.

    “where competition for limited Fe resources emerged as an evolutionary conserved host defense strategy against infection in plants (2) and animals (3–5) as well as a microbial virulence factor (6).”

    From Innate Nutritional Immunity (2018) · cites this paper as [6]

  • Siderophores are paired with specific microbial receptors that capture iron-siderophore complexes and enable microbial iron uptake.

    “These are coupled to specific microbial receptors that capture Fe-siderophore complexes and allow for microbial Fe acquisition (6) (Figure 1).”

    From Innate Nutritional Immunity (2018) · cites this paper as [6]

  • Pathogenic microbes evolved diverse efficient ways to obtain iron from hosts and thereby overcome nutritional immunity.

    “Likewise, pathogenic microbes co-evolved to deploy diverse and efficient mechanisms to acquire Fe from their hosts and in doing so overcome nutritional immunity.”

    From Innate Nutritional Immunity (2018) · cites this paper as [6]

  • Most pathogens evolved ways to divert host iron into their own metabolism, while hosts evolved ways to restrict pathogen iron access.

    “Presumably, this explains why most pathogens evolved a variety of strategies aimed at diverting Fe from their hosts into their own metabolic pathways, while hosts co-evolved strategies to restrict pathogens from accessing Fe (3–6).”

    From Innate Nutritional Immunity (2018) · cites this paper as [6]

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Newberne PM, 1968, Br. J. Exp. Pathol., 49, 448
  2. Van Valen L, 1973, Evol. Theory, 1, 1

Cited by

Sorted by citations

Related

Authors
Palmer, L. D., & Skaar, E. P.
Affiliations
  • Vanderbilt University Medical Center (US)
  • VA Tennessee Valley Healthcare System (US)
Corresponding author
Skaar, Eric P.
ORCID
Venue
Annual Review of Genetics
Publisher
Annual Reviews
Published
2016-11-23
Volume
50
Issue
1
Pages
67-91
ISSN
  • 0066-4197 (ISSN-L)
  • 1545-2948
DOI
10.1146/annurev-genet-120215-035146
PMC
PMC5125913
OpenAlex
W2346357109
Semantic Scholar
3500f44363afc7e63fe0fef4bc89f9e31be95e72
Cited by
449
References
150
Citations by year
2026: 43 · 2025: 54 · 2024: 41 · 2023: 55 · 2022: 42 · 2021: 65 · 2020: 47 · 2019: 42 · 2018: 38 · 2017: 21 · 2016: 1
FWCI
4.54
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01 BX002482)
  • American Asthma Foundation
  • National Institutes of Health
  • Advanced Research Projects Agency
  • National Heart, Lung, and Blood Institute (T32HL094296)
  • National Institute of General Medical Sciences (T32GM008320)
  • National Institute of Allergy and Infectious Diseases (F32AI122516, R01AI069233, R01AI101171, R21AI107233)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
transition metals, bacterial virulence, host-pathogen interaction, metal acquisition, metal sequestration, metal toxicity, host specificity, host-pathogen coevolution, rapid evolution, trace elements
MeSH terms
Animals, Bacteria, Bacterial Infections, Deficiency Diseases, Diet, Heme, Humans, Iron, Metals, Siderophores, Iron Overload, Host-Pathogen Interactions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

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