Role of Nickel in Microbial Pathogenesis Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Read MoreKaren 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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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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Karen Pendergrass
Read More -
Dr. Umar
Read More
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Read More -
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.
Karen Pendergrass
What was reviewed?
This review examined nickel in microbial pathogenesis, focusing on how nickel-dependent enzymes shape virulence across bacteria, fungi, and select protozoa. Nickel in microbial pathogenesis emerges as a central theme because pathogens rely heavily on nickel-requiring enzymes—particularly urease and [NiFe]-hydrogenases—to survive hostile host environments, acquire nutrients, and drive energy metabolism. Using mechanistic, genomic, and in vivo evidence, the paper synthesizes findings across more than forty prokaryotic and nine eukaryotic pathogens, emphasizing how nickel scarcity within the host constrains microbial physiology and selects for specialized uptake, storage, and trafficking systems. The review also integrates structural insights, host nutritional immunity, and emerging metallophore pathways, illustrating how nickel availability shapes pathogenic strategies and may represent a therapeutic vulnerability.
Who was reviewed?
The review covered a wide spectrum of microbial taxa, including gastric Helicobacter species, enteric bacteria such as Salmonella and Shigella, uropathogens like Proteus, Klebsiella, and Staphylococcus species, as well as fungal pathogens including Cryptococcus and Coccidioides. These organisms possess nickel-requiring enzymes used for acid resistance, nitrogen acquisition, energy generation, oxidative stress defense, or metabolic detoxification. Some protozoan parasites—including Leishmania and Trypanosoma—were discussed for their nickel-dependent glyoxalase systems. The organisms reviewed represent pathogens inhabiting diverse niches such as the stomach, urinary tract, respiratory tract, bloodstream, skin, macrophages, and central nervous system, with nickel biochemistry serving as a shared determinant of successful host colonization.
Most important findings
Nickel-dependent urease and [NiFe]-hydrogenases are the most influential virulence factors. Urease enables pathogens like Helicobacter pylori, Proteus mirabilis, and Cryptococcus neoformans to neutralize acidic environments through ammonia production; in urinary pathogens, this activity drives stone formation and biofilm-associated persistence. In H. pylori, urease also performs noncatalytic antioxidant functions tied to methionine-sulfoxide cycling. Hydrogenases fuel pathogenic energy metabolism: H. pylori uses hydrogen to power CO₂ fixation and energize CagA oncoprotein delivery. Enteric pathogens like Salmonella Typhimurium require multiple hydrogenases for gut colonization and intracellular survival. Additional nickel enzymes—Ni-glyoxalase I, Ni-superoxide dismutase, and Ni-acireductone dioxygenase—contribute to methylglyoxal detoxification, oxidative stress defense, and methionine salvage. A major theme is host-driven nickel limitation via calprotectin, lactoferrin, and hepcidin, which pressures pathogens to evolve high-affinity uptake systems (NikABCDE, NixA, NiCoT), metallophores such as staphylopine and pseudopaline, and histidine-rich storage proteins (Hpn, Hpnl) that buffer nickel and coordinate enzyme maturation. This interplay between host nutritional immunity and pathogen nickel acquisition emerges as a defining microbiome-relevant axis.
| Nickel-associated factor | Microbiome-relevant pathogenic impact |
|---|---|
| Urease (e.g., H. pylori, P. mirabilis) | Acid neutralization, ammonia-driven dysbiosis, stone formation supporting polymicrobial biofilms |
| [NiFe]-Hydrogenases (e.g., H. pylori, Salmonella) | Hydrogen-dependent energy metabolism enhancing colonization, intracellular survival, and toxin delivery |
| Nickel uptake and metallophore systems | Competitive advantage within the microbiome through enhanced metal scavenging and enzyme activation |
| Nickel-storage proteins (Hpn, Hpnl) | Stabilization of enzyme maturation under metal scarcity, supporting long-term persistence in mucosal niches |
Key implications
The review highlights nickel as a crucial microbial resource absent from mammalian biochemistry—creating an exploitable therapeutic gap. Targeting nickel uptake or storage could cripple multiple virulence pathways simultaneously, especially in pathogens highly dependent on urease and hydrogenase activity. Because commensal microbiota also use nickel enzymes, the review underscores the need for microbiome-aware therapeutic design. Nickel availability may shape microbial community structure, pathogen competition, and disease susceptibility. Understanding nickel-dependent signatures could enhance microbiome profiling, pathogen detection, and biomarker discovery.
Citation
Maier RJ, Benoit SL. Role of nickel in microbial pathogenesis. Inorganics. 2019;7(7):80. inorganics-07-00080