Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
The review Role of Nickel in Microbial Pathogenesis explores how nickel-dependent enzymes, transporters, and storage proteins support microbial virulence. It highlights key Ni enzymes (urease, [NiFe]-hydrogenases) and less common Ni enzymes, details Ni uptake pathways, and discusses host defense strategies restricting Nickel.
Who was reviewed?
The authors reviewed a broad taxonomic set: ~40 prokaryotic and 9 eukaryotic pathogens with documented or predicted Ni-requiring systems. Key organisms extensively discussed include Helicobacter pylori and related Helicobacter spp. (gastric and hepatic pathogens), enteric pathogens such as Salmonella Typhimurium and Shigella spp., urinary pathogens like Proteus mirabilis and Morganella, skin and device-associated Staphylococcus spp., environmental/foodborne agents like Campylobacter jejuni, and fungal pathogens including Cryptococcus neoformans and C. gattii. The review also surveys Ni-dependent enzymes across bacterial phyla (Proteobacteria, Firmicutes, Actinobacteria, Mollicutes) and protozoan parasites (e.g., Leishmania, Trypanosoma), capturing evidence from genetic knockouts, in vivo animal infection models, biochemical characterization, and genomic predictions.
Most important findings
The review identifies two Ni-enzymes as repeatedly central to virulence: urease and [NiFe]-hydrogenases. Urease activity confers acid resistance, nitrogen acquisition, and local pH shifts that drive urinary stone formation and crystalline biofilms (e.g., P. mirabilis, uropathogens), while in H. pylori, urease supports stomach colonization, persistence, immune modulation, and contributes to carcinogenic processes.
| Aspect | Key Details | Pathogen examples |
|---|---|---|
| Urease | Acid resistance, urea hydrolysis, urinary stone formation, crystalline biofilms | H. pylori, Proteus mirabilis |
| [NiFe]-Hydrogenases | Calprotectin, lactoferrin, and NRAMP1 sequester Ni to block pathogen enzymes | H. pylori, S. Typhimurium |
| Other Ni Enzymes | Ni-ARD (methionine salvage), Ni–GloI (methylglyoxal detox), Ni-SOD (ROS defense) | Klebsiella, Cryptococcus |
| Ni Uptake Systems | Nickelophores, TonB-dependent uptake, ABC and NiCoT transporters | H. pylori, C. jejuni |
| Ni Storage & Maturation | Hpn/Hpn-like storage proteins, HypA/B and UreE chaperones | H. pylori, Proteus spp. |
| Host Defense | Calprotectin, lactoferrin, NRAMP1 sequester Ni to block pathogen enzymes | Mammalian hosts |
Key implications
For HTMC, Ni exposure has microbial relevance: pathogens depend on Ni enzymes for survival, while host defenses restrict Ni to fight infection. Certification should assess not only total Ni but also bioavailability in consumer products, water, and foods. Regulatory efforts could align with anti-virulence strategies targeting Ni uptake.
Citation
Maier RJ, Benoit SL. Role of Nickel in Microbial Pathogenesis. Inorganics. 2019;7(7):80. doi:10.3390/inorganics7070080.
Nickel is a widely used transition metal found in alloys, batteries, and consumer products that also contaminates food and water. High exposure is linked to allergic contact dermatitis, organ toxicity, and developmental effects, with children often exceeding EFSA’s tolerable daily intake of 3 μg/kg bw. Emerging evidence shows nickel crosses the placenta, elevating risks of preterm birth and congenital heart defects, underscoring HMTC’s stricter limits to safeguard vulnerable populations.
