Maier and Benoit 2019 — Role of Nickel in Microbial Pathogenesis
This MDPI Inorganics review by Robert Maier and Stéphane Benoit (University of Georgia, Center for Metalloenzyme Studies) synthesizes the mechanistic literature on nickel-dependent virulence factors in human and animal pathogens. The review covers the [NiFe] hydrogenase and urease enzyme families, with particular depth on Helicobacter pylori (the gastric pathogen most heavily dependent on Ni for both H2-utilization-driven host colonization and translocation of the carcinogenic CagA toxin into host epithelial cells). Salmonella enterica Typhimurium hydrogenases are characterized as host-colonization factors; Proteus mirabilis, Staphylococcus species, and Cryptococcus genus ureases are reviewed as pathogenesis components in urinary-tract, soft-tissue, and meningeal infections respectively. The authors document the pathogen Ni-uptake, Ni-storage, and Ni-maturation enzyme machinery that supports the virulence-relevant Ni utilization.
Key conclusions
Pathogens depend on Ni for specific virulence-associated enzymes and have evolved sophisticated transporters, storage reservoirs, and maturation systems to balance Ni availability against Ni toxicity. The review documents at least five distinct pathogen-Ni-virulence systems: Helicobacter pylori H2-utilization-driven colonization; H. pylori urease for gastric pH neutralization; Salmonella Typhimurium [NiFe] hydrogenases; Proteus mirabilis urease for urolithiasis pathogenesis; Cryptococcus species urease for blood-brain-barrier penetration. Host nutritional immunity (calprotectin-mediated Ni and Zn sequestration) is the principal evolutionary counter to pathogen Ni acquisition.
Implications
- Certification: Background context for why dietary and ambient Ni matters beyond its direct host toxicity. Even sub-clinical dietary Ni can perturb pathogen virulence in ways the EFSA TDI does not directly address.
- Microbiome: Foundational for the Ni-microbiome-pathogenesis crosswalk to WikiBiome. Establishes that Ni is not merely a host toxicant but a pathogen virulence cofactor with implications for gastric, urinary-tract, and central-nervous-system infections.
- Courses: Standard teaching reference for the metallobiology of pathogenesis.