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镍作为 I 类细菌致癌因子幽门螺杆菌的毒力因子。

Nickel as a virulence factor in the Class I bacterial carcinogen, Helicobacter pylori.

机构信息

Department of Chemistry and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA, 01003, USA.

Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, I-40127, Bologna, Italy.

出版信息

Semin Cancer Biol. 2021 Nov;76:143-155. doi: 10.1016/j.semcancer.2021.04.009. Epub 2021 Apr 15.

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.

摘要

幽门螺杆菌是一种人类细菌病原体,可导致消化性溃疡,并被国际癌症研究机构 (IARC) 列为 I 类致癌物。其在胃酸环境中生存、定植于胃黏膜并导致癌症的能力与两种需要镍脲酶和氢化酶的酶有关。因此,镍是一种重要的毒力因子,涉及镍转运的蛋白质是潜在的抗生素靶标。本综述总结了幽门螺杆菌的镍生物化学,重点介绍了镍在毒力、镍稳态、脲酶和氢化酶成熟以及发生在氢化酶成熟途径和脲酶镍掺入之间的独特镍转运中的作用,这种转运是由金属伴侣蛋白 HypA 及其伴侣 HypB 介导的。

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