包膜应激响应蛋白CpxA突变及其对细菌耐药性和毒力的调控

Mutation of the envelope stress-responsive protein CpxA capable of regulating the antimicrobial resistance and virulence of bacteria

摘要:

CpxA是革兰氏阴性细菌中普遍存在的包膜双组分系统Cpx的关键成员，负责信号感应，兼具磷酸酶和激酶双重活性，参与多种细菌耐药及致病性等重要生理过程的调控。近年来，靶向CpxA的新型抗菌药物开发引起研究者的关注，基于其磷酸酶活性抑制功能的药物在大肠杆菌所致尿路感染的治疗中初显成效。本文梳理了细菌包膜应激感应蛋白CpxA的结构、功能域及其激活CpxR的通路，总结分析了其参与细菌耐药性形成及毒力调控的机制，同时综述了当前针对该靶点研发的抗菌药物的最新进展，以期助力临床严重耐药菌抗感染治疗新策略的研发。

Abstract:

CpxA is a key member of the envelope stress-responsive Cpx two-component system ubiquitous in Gram-negative bacteria. It is responsible for signal sensing and has dual activities of phosphatase and kinase. CpxA has been revealed to participate in the regulation of physiological processes such as virulence and antimicrobial resistance of bacteria. In recent years, the development of novel antimicrobials targeting CpxA has attracted much attention. Drugs developed based on inhibition of the phosphatase activity of CpxA have shown effectiveness in the treatment of urinary tract infections caused by Escherichia coli. This review introduces the structure and functional domains of CpxA and the activation of Cpx pathways by CpxA. Furthermore, it summarizes the roles of CpxA in the development of antimicrobial resistance and the regulation of bacterial virulence and reviews the latest progress in the development of new antimicrobials targeting this protein. It is expected to assist in the exploration of CpxA-targeting anti-infection strategies for severely antimicrobial-resistant bacteria whose clinical infections are of urgent need to be controlled.