The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity Original paper
Researched by:
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Divine Aleru
ID
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.
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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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Divine Aleru
Read More
Researched by:
-
Divine Aleru
ID
Divine Aleru
Read More
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.
Divine Aleru
What was studied?
This study explored how Staphylococcus aureus acquires zinc during infection and competes with the host’s immune system for this critical metal. The research identified the role of two zinc import systems—AdcABC and CntABCDF—and the metallophore staphylopine in zinc acquisition. It also investigated how these systems allow the pathogen to resist host-imposed zinc starvation, a component of the host’s nutritional immunity.
Who was studied?
The study primarily focused on Staphylococcus aureus and its ability to acquire and utilize zinc during infection. Researchers used wild-type and mutant strains of S. aureus lacking key zinc transporters (AdcABC, CntABCDF) and the metallophore staphylopine (StP) to assess their role in overcoming host-imposed zinc starvation.
What were the most important findings?
The study identified that S. aureus utilizes two distinct zinc import systems: the AdcABC system and the CntABCDF system. While the AdcABC system has been previously associated with zinc uptake in other bacteria, the CntABCDF system, along with the metallophore staphylopine (StP), was shown to be critical for zinc acquisition during infection. Loss of either the Cnt system or StP severely impaired S. aureus’ ability to grow in zinc-limited conditions and diminished its ability to resist the immune effector calprotectin (CP), which restricts metal availability. Interestingly, the Cnt system was primarily responsible for S. aureus‘s ability to compete with CP for zinc, while the AdcABC system did not play a significant role in this competition. The metallophore staphylopine was found to function similarly to siderophore-based iron acquisition systems, facilitating the uptake of zinc via the Cnt system. Additionally, the study showed that the Cnt-StP system is the dominant zinc acquisition pathway used by S. aureus during systemic infection in mice, with mutants lacking this system showing reduced bacterial burden and virulence.
What are the greatest implications of this study?
The findings of this study have important implications for understanding how S. aureus and other pathogens overcome the host’s nutritional immunity. By identifying the Cnt-StP system as a key player in zinc acquisition, the research offers insights into new strategies for disrupting bacterial infection. Targeting zinc acquisition systems like Cnt-StP could provide a novel approach to antimicrobial therapy, especially for infections where zinc limitation plays a crucial role in the host defense. Moreover, the discovery of staphylopine analogs in other bacterial pathogens suggests that this system might be broadly applicable in bacterial pathogenesis, potentially opening up new avenues for therapeutic intervention across a range of infections.