双组分调控系统介导革兰阴性菌耐药的作用机制

doi:10.11843/j.issn.0366-6964.2022.06.004

摘要/Abstract

摘要： 菌群耐药已成为临床上亟待解决的关键问题，特别是革兰阴性菌引起的耐药现象尤为突出，给临床治疗带来了巨大的挑战，尽快阐明重要细菌复杂耐药表型的调控机制就显得尤为重要。双组分调控系统(two-component regulatory systems，TCS)存在于多种革兰阴性菌中，在细菌诸多生命活动中发挥关键作用，是细菌感知环境变化并产生相应调控的主要机制之一。TCS通常由两种蛋白组成，包括感受器蛋白(通常是组氨酸激酶)和反应调节蛋白(通常是转录因子)，二者可通过磷酸化介导的协同作用，整合细菌周围的环境信号、调节细菌相关的基因表达及改变细菌的某些生理行为。近年来，探索细菌TCS介导的耐药性应答机制已成为一个新的研究热点。基于此，本文从TCS介导临床重要革兰阴性菌耐药的结构基础和作用机理等方面进行综述，以期增进对细菌TCS的全面认识，为今后临床上药物的科学研发提供新的思路和对策。

关键词: 双组分调控系统(TCS), 刺激信号, 细菌耐药, 转录调控

Abstract: Bacterial resistance has become a key problem to be solved in clinical practice, especially the drug resistance caused by Gram-negative bacteria, which bring great challenges to clinical treatment. It is particularly important to clarify the regulatory mechanism of complex drug resistance phenotypes of important bacteria as soon as possible. Two-component regulatory systems (TCS) exist in a variety of Gram-negative bacteria and play important roles in the life activities of bacteria. TCS is one of the principal mechanisms by which bacteria perceive environmental changes and produce corresponding regulations. TCS is usually composed of two proteins, including sensor proteins (usually histidine kinases) and responsive regulatory proteins (usually transcription factors). Both of them can integrate the environmental signals of bacteria, regulate gene expression and change the physiological behavior of bacteria through phosphorylation-mediated synergy. The response mechanism studies of TCS-mediated drug resistance have become a new research hotspot recently. In this paper, the structural basis and mechanism of TCS-mediated drug resistance of clinically important Gram-negative bacteria were reviewed. It would be enhancing the comprehensive understanding of the bacterial TCS system and provide new ideas and strategies for the scientific research and development of drugs in the future.

Key words: two-component regulatory systems (TCS), stimulus signal, bacterial drug resistance, transcriptional regulation

中图分类号:

S852.61

于永峰, 权衡, 董文豪, 邹荣华, 吴晓妮, 宫晓炜, 陈启伟. 双组分调控系统介导革兰阴性菌耐药的作用机制[J]. 畜牧兽医学报, 2022, 53(6): 1689-1701.

YU Yongfeng, QUAN Heng, DONG Wenhao, ZOU Ronghua, WU Xiaoni, GONG Xiaowei, CHEN Qiwei. The Mechanism of Two-component Regulatory System Mediating Drug Resistance of Gram-negative Bacteria[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(6): 1689-1701.

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