Nutrient Metal Sequestration by Calprotectin Inhibits Bacterial Superoxide Defense, Enhancing Neutrophil Killing of Staphylococcus aureus Original paper
Researched by:
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Divine Aleru
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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.
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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 investigated the role of calprotectin, a neutrophil protein, in enhancing the killing of Staphylococcus aureus by sequestering manganese (Mn) and zinc (Zn), which are essential metals for bacterial defense mechanisms. The study particularly focused on how calprotectin’s sequestration of these metals inhibits bacterial superoxide defense systems, thereby increasing the susceptibility of S. aureus to the immune response.
Who was studied?
The study primarily involved Staphylococcus aureus, including both wild-type strains and mutants deficient in superoxide dismutases (SODs), which are crucial for bacterial defense against oxidative stress. The research was conducted using in vitro assays and in vivo murine models to observe the effects of calprotectin on S. aureus growth and virulence.
What were the most important findings?
The study found that calprotectin, through its ability to bind manganese and zinc, significantly enhances the sensitivity of S. aureus to superoxide stress. Calprotectin sequesters these metals, disrupting bacterial superoxide defense mechanisms, particularly the manganese-dependent superoxide dismutases (SODs) in S. aureus. This metal sequestration leads to elevated superoxide levels within the bacteria, making them more susceptible to neutrophil killing. The research demonstrated that calprotectin’s antimicrobial effects were directly linked to its ability to chelate metal ions, as mutations in calprotectin that impaired metal binding abolished its antimicrobial properties. Moreover, calprotectin increased the sensitivity of S. aureus to superoxide stress and neutrophil-mediated killing in both exponential and stationary bacterial phases.
What are the greatest implications of this study?
This study has significant implications for understanding how the immune system utilizes nutrient metal sequestration to combat infections. The findings emphasize the role of calprotectin in enhancing immune defense by making bacterial pathogens more vulnerable to oxidative stress, thus improving the effectiveness of neutrophils in clearing infections. The study also suggests that targeting metal ion acquisition in pathogens could be a potential therapeutic strategy, offering a new avenue for antimicrobial treatments, especially against S. aureus and other pathogens that rely on metal-dependent defenses.
Calprotectin
Calprotectin is a neutrophil-derived protein complex measured in stool to detect intestinal inflammation. It helps distinguish IBD from functional bowel disorders and reflects mucosal immune activity that can reshape microbiome composition through antimicrobial metal sequestration.
Manganese (Mn)
Manganese plays a pivotal role in microbial pathogenesis. As a vital cofactor for enzymes involved in antioxidant defense and metabolism, manganese is essential for pathogens, enabling them to survive within the host. However, when not properly managed, manganese can become toxic to both the host and the pathogen. The host’s immune system, through mechanisms like the secretion of calprotectin, tries to limit microbial access to manganese, creating an ongoing battle between host defenses and microbial survival .
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.