Transition metals and virulence in bacteria Original paper
Researched by:
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Dr. Umar
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Dr. Umar
Read MoreClinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
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Metals
Metals
Heavy metals play a significant and multifaceted role in the pathogenicity of microbial species.
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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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Dr. Umar
Read More
Researched by:
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Dr. Umar
ID
Dr. Umar
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.
Dr. Umar
What was reviewed?
This review article examines how transition metals shape bacterial virulence through three interconnected processes: acquisition, limitation, and intoxication. It emphasizes the evolutionary “arms race” between microbial strategies for metal uptake and host mechanisms for nutritional immunity. The review highlights how iron, zinc, and manganese—critical cofactors for bacterial metabolism—are sequestered, restricted, or weaponized by the host to control infection. It also explores the concept of transition metals and virulence in bacteria as a core microbiome-relevant signature, demonstrating how microbial metal-utilization pathways structure pathogen behavior, niche occupation, and survival. The article integrates molecular mechanisms, structural biology, host–pathogen coevolution, and ecological microbiology to reveal how elemental micronutrients act as regulators of infection outcomes.
Who was reviewed?
The review encompasses bacterial pathogens across Gram-positive and Gram-negative lineages, including Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Mycobacterium tuberculosis, Salmonella enterica, Yersinia spp., and Helicobacter pylori. Host mechanisms are also examined, particularly actions performed by neutrophils, macrophages, epithelial cells, and the proteins lipocalin-2, calprotectin, transferrin, and lactoferrin. The focus spans vertebrate immune systems broadly, highlighting conserved strategies used by mammals to alter microbial metal access. Together, the reviewed organisms illustrate how microbial metal acquisition systems both shape and respond to selective pressures across human tissues and microbiome-related environments.
Most important findings
A key finding is that metal competition constitutes a major determinant of bacterial virulence. Iron is strictly limited by the host, leading pathogens to evolve siderophores, heme-capture systems, and metal piracy mechanisms. Zinc and manganese restriction—driven by proteins such as calprotectin—is shown to profoundly suppress bacterial metabolic capacity. Conversely, hosts deploy toxic levels of copper and zinc within phagolysosomes, weaponizing mismetallation and oxidative chemistry. The review also identifies new microbial strategies such as stealth siderophores, zincophore secretion, and broad-spectrum metallophores like staphylopine. These systems demonstrate microbiome-relevant metal signatures: siderophore repertoires, manganese import profiles, and metal efflux capacity mark virulence traits.
| Concept | Key Microbiome-Relevant Insight |
|---|---|
| Siderophores & piracy | Distinct siderophore families define pathogen niche fitness and resistance to host sequestration. |
| Calprotectin activity | Multimetal sequestration rewires microbial community dynamics and infection severity. |
| Metal intoxication | Copper/zinc delivery by phagocytes creates selective pressures shaping pathogen genomes. |
| Host metal dysregulation | Iron overload and zinc deficiency shift microbial virulence factor expression and disease risk. |
Key implications
Understanding microbial metal utilization enables prediction of pathogen behavior in metal-variable environments, including the gut, lung, and urinary tract. Metal signatures—such as siderophore type, heme uptake pathways, and zinc/manganese transport profiles—may serve as biomarkers for virulence potential and microbiome destabilization. The review suggests therapeutic avenues that bypass traditional antibiotic targets, including siderophore decoys, gallium-based metal substitution strategies, and vaccines against metal acquisition systems. It also highlights how dietary metal intake and host genetic variations influence infection susceptibility, emphasizing the need to integrate metal homeostasis into microbiome-focused clinical decision-making.
Citation
Palmer LD, Skaar EP. Transition metals and virulence in bacteria.Annual Review of Genetics. 2016;50:67-91. doi:10.1146/annurev-genet-120215-035146
Staphylococcus aureus (S. Aureus)
Staphylococcus aureus is a versatile skin and mucosal commensal that can transition into a highly virulent pathobiont. Known for its immune-evasive strategies, toxin production, and antibiotic resistance, it plays a significant role in chronic infections and microbiome imbalance.