Role of Nickel in Microbial Pathogenesis

Abstract

Nickel is an essential cofactor for some pathogen virulence factors. Due to its low availability in hosts, pathogens must efficiently transport the metal and then balance its ready intracellular availability for enzyme maturation with metal toxicity concerns. The most notable virulence-associated components are the Ni-enzymes hydrogenase and urease. Both enzymes, along with their associated nickel transporters, storage reservoirs, and maturation enzymes have been best-studied in the gastric pathogen Helicobacter pylori, a bacterium which depends heavily on nickel. Molecular hydrogen utilization is associated with efficient host colonization by the Helicobacters, which include both gastric and liver pathogens. Translocation of a H. pylori carcinogenic toxin into host epithelial cells is powered by H2 use. The multiple [NiFe] hydrogenases of Salmonella enterica Typhimurium are important in host colonization, while ureases play important roles in both prokaryotic (Proteus mirabilis and Staphylococcus spp.) and eukaryotic (Cryptoccoccus genus) pathogens associated with urinary tract infections. Other Ni-requiring enzymes, such as Ni-acireductone dioxygenase (ARD), Ni-superoxide dismutase (SOD), and Ni-glyoxalase I (GloI) play important metabolic or detoxifying roles in other pathogens. Nickel-requiring enzymes are likely important for virulence of at least 40 prokaryotic and nine eukaryotic pathogenic species, as described herein. The potential for pathogenic roles of many new Ni-binding components exists, based on recent experimental data and on the key roles that Ni enzymes play in a diverse array of pathogens.

Influence of Protein Glycosylation on Campylobacter fetus Physiology

“…Our research connects N-glycosylation to HynABC hydrogenase regulation and nickel/iron homeostasis, two cellular processes which have been associated with pathogenicity in other bacteria (Palyada et al, 2004;Maier and Benoit, 2019;Benoit et al, 2020). The presented results deepen our understanding of the role of N-glycosylation in C. fetus cell physiology.…”

The structure-based reaction mechanism of urease, a nickel dependent enzyme: tale of a long debate

“…This alkalization effect is utilized by numerous human pathogenic microorganisms that exploit urease as a virulence factor to infect and colonize the host [7,9,10]. The priority pathogen list indicated by the World Health Organization for the research and development of new antibiotics [11] includes urease-dependent antibiotic-resistant bacteria, several of which are involved in bacterial infections of the respiratory apparatus, and it is remarkable that half of patients who died of the recent COVID-19 epidemics in Wuhan (China) became co-infected with bacteria in the lungs and also required antibiotics [12].…”

Inhibition of Urease, a Ni‐Enzyme: The Reactivity of a Key Thiol With Mono‐ and Di‐Substituted Catechols Elucidated by Kinetic, Structural, and Theoretical Studies

“…[2] This reaction causes an overall increase of pH that has negative consequences for both human health [3] and the environmental ecosphere. [4] In particular, urease is exploited as av irulence factor by several human pathogens [3,5] including Helicobacter pylori, [6] Staphylococcus aureus, [7] Mycobacterium tuberculosis, [8] Yersinia enterocolitica [9] and Cryptococcus neoformans, [10] thus acting as at hreat to public health worldwide. Moreover,t he priority pathogen list indicated by the World Health Organization for the research and development of new antibiotics includes several urease-dependent antibioticresistant bacteria, many of which are involved in bacterial infections of the respiratory apparatus.…”