Metallophores Drive Staphylococcus aureus Virulence and Pathogenicity Original paper
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was reviewed?
This review article comprehensively examined the role of metallophores in the pathogenicity and virulence of Staphylococcus aureus, emphasizing their molecular structures, biosynthetic pathways, transport mechanisms, and regulatory systems. The authors detail the distinct types of metallophores produced by S. aureus—including staphyloferrin A, staphyloferrin B, staphylobactin, aureochelin, and the broad-spectrum staphylopine—highlighting their importance in overcoming host nutritional immunity during infection.
Who was reviewed?
The review synthesizes data from numerous studies involving both in vitro and in vivo models, including murine infection systems. It primarily focuses on Staphylococcus aureus as a pathogen, but also references bacterial competitors and host immune responses to illustrate how metallophores enable S. aureus to outcompete other microbes and evade host defenses.
Most important findings
Metallophores are crucial for S. aureus to acquire essential metal ions under host-imposed metal-limiting conditions. The review identifies two primary iron-chelating siderophores (staphyloferrin A and B), a hydroxamate-type siderophore (staphylobactin), and the less-characterized aureochelin. Staphylopine, a nicotianamine-like opine metallophore, is distinguished by its ability to chelate multiple metals, including zinc and nickel. The regulation of metallophore systems is tightly controlled by metal-responsive regulators Fur and Zur. Notably, staphylopine acts as a zincophore, essential in zinc-limited environments. S. aureus also imports xenosiderophores produced by other microbes, further enhancing its adaptability and virulence.
Table: Summary of S. aureus Metallophores
| Metallophore | Metal Target(s) | Regulatory Proteins | Transporter |
|---|---|---|---|
| Staphyloferrin A | Iron | Fur | HtsABC |
| Staphyloferrin B | Iron | Fur | SirABC |
| Staphylobactin | Iron | Fur | SirABC |
| Aureochelin | Iron (phenolate/catecholate) | Unknown | Unknown |
| Staphylopine | Zn, Ni, Co, Cu, Fe (broad) | Fur and Zur | CntABCDF, CntE export |
Key implications
Understanding the metallophore-mediated metal acquisition systems of S. aureus reveals critical virulence mechanisms that could be therapeutically targeted. Disrupting these systems—especially the staphylopine pathway—could impair bacterial fitness under nutrient-limited conditions, attenuate virulence, and enhance susceptibility to host immune defenses. The insights into regulatory systems (Fur/Zur) and unique transporters also pave the way for antimicrobial strategies that block metallophore synthesis or function without relying on traditional antibiotics.
Zinc
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.