Mechanistic insights into staphylopine-mediated metal acquisition Original paper
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Metals
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Microbes
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types—bacteria, viruses, fungi, protozoa, and archaea—plus major pathogenic and beneficial examples.
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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.
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
What was studied?
This study investigated the mechanism by which Staphylococcus aureus utilizes staphylopine (StP), a metallophore, to acquire transition metals during infection. Specifically, it focused on the CntA protein, a component of the StP/metal transport system, and how it recognizes and transports StP-bound metals such as Co²⁺, Ni²⁺, and Zn²⁺. The researchers explored the detailed structural and biochemical interactions between StP, metals, and CntA, as well as how these interactions are critical for bacterial virulence.
Who was studied?
The study primarily examined Staphylococcus aureus and its StP/metal acquisition system, particularly the role of the CntA protein in metal recognition and transport. It also involved other proteins related to the StP-mediated metal transport system, such as CntB, CntC, and CntD, and investigated their roles in virulence. Additionally, the study explored the effects of mutations in specific amino acids of CntA to assess their impact on metal acquisition and bacterial fitness.
What were the most important findings?
The study revealed the detailed mechanism by which S. aureus acquires transition metals via the staphylopine system. It was determined that CntA, a solute-binding protein (SBP), plays a critical role in recognizing and binding to StP/metal complexes. Structural analysis showed that binding of metals such as Co²⁺, Ni²⁺, and Zn²⁺ to StP induced a conformational change in CntA, which is essential for the subsequent transport of these metals into the bacterial cell. The study also identified key amino acid residues involved in metal recognition, such as arginine and tryptophan residues, which play a primary role in metal binding and facilitate the transport process. Furthermore, the researchers demonstrated that the StP/metal recognition mechanism is crucial for S. aureus‘s ability to grow under metal-limited conditions, such as those imposed by host immune proteins like calprotectin. Mutations in critical residues of CntA impaired the bacterium’s ability to acquire metal and reduced its growth and virulence, highlighting the importance of StP-mediated metal acquisition for bacterial fitness.
What are the greatest implications of this study?
The findings of this study have significant implications for understanding how S. aureus and other pathogens acquire essential metals during infection. By identifying the key role of the CntA-mediated StP/metal recognition system in metal homeostasis, this research provides new targets for antimicrobial therapies aimed at disrupting bacterial metal acquisition. Inhibiting this system could reduce bacterial virulence by limiting metal availability, an approach that could be particularly useful in treating infections caused by S. aureus. The study also adds to the broader understanding of bacterial strategies to evade host-imposed nutritional immunity, where pathogens compete with the host for metals like zinc and iron.