Nickel as a virulence factor in the Class I bacterial carcinogen, Helicobacter pylori
Michael J Maroney1, Stefano Ciurli2
1Department of Chemistry and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA, 01003, USA.
Abstract:
Helicobacter pylori is a human bacterial pathogen that causes peptic ulcers and has been designated a Class I carcinogen by the International Agency for Research on Cancer (IARC). Its ability to survive in the acid environment of the stomach, to colonize the stomach mucosa, and to cause cancer, are linked to two enzymes that require nickel-urease and hydrogenase. Thus, nickel is an important virulence factor and the proteins involved in nickel trafficking are potential antibiotic targets. This review summarizes the nickel biochemistry of H. pylori with a focus on the roles of nickel in virulence, nickel homeostasis, maturation of urease and hydrogenase, and the unique nickel trafficking that occurs between the hydrogenase maturation pathway and urease nickel incorporation that is mediated by the metallochaperone HypA and its partner, HypB.
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