摘要
细菌对药物产生耐药性的机制多种多样,主动外排(efflux)是重要和常见的耐药机制之一.主动外排过程是细菌不同种类的外排蛋白系统将药物从自身体内主动外泵排出的过程.主动外排耐药机制属于非特异性耐药机制,具有底物广、能量依赖、外排泵种类多和外排泵来源菌多的特点.外排泵广泛存在于革兰阳性菌、革兰阴性菌和分枝杆菌中,因此抑制耐药细菌的一条重要途径是寻找和发现外排泵抑制剂.外排泵抑制剂通过抑制外排泵对抗生素药物的外排作用,从而恢复细菌对抗生素的敏感性.外排泵抑制剂可根据所作用的外排泵能量来源不同分为ATP水解能驱动型外排泵抑制剂和跨膜质子梯度能驱动型外排泵抑制剂两大类;也可依据所抑制的外排泵蛋白种类不同分为NorA蛋白抑制剂,Mex外排泵抑制剂,Tet(B)外排泵抑制剂,以及AcrAB-TolC外排泵抑制剂等多种类型.各种类型的外排泵抑制剂将成为解决细菌耐药问题的有效方法之一.
The mechanisms of bacterial drug resistance were various. One of the most important and common mechanisms is active efflux system of bacteria. During the process of efflux, different kinds of efflux protein could discharge drugs initiatively. The active efflux belongs to nonspecific resistant mechanism, with the features of substrate universality, energy dependence, species and source diversity. Efflux pumps are widely found in Gram-positive bacteria, Gram-negative bacteria and Mycobacteria . Finding efflux pump inhibitors is an important way to inhibit drug-resistant bacteria because they could restore bacterial sensitivity to antibiotics by inhibiting the efflux effects of bacteria. The efflux pump inhibitors can be divided into two categories according to their energy sources: ATP hydrolytic energy driven efflux pump inhibitors and transmembrane proton gradient energy driven efflux pump inhibitors. They can also be classified as NorA protein inhibitors, Mex, Tet(B), AcrAB-TolC, et al efflux pump inhibitors according to the type of the efflux pump protein inhibited. Various types of efflux pump inhibitors will be one of the effective methods to overcome bacterial drug resistance.
作者
孙仲琳
崔锦
王锐
穆青
SUN Zhonglin;CUI Jin;WANG Rui;MU Qing(School of Pharmacy, Fudan University, Shanghai 201203, China;Zhaotong College, Zhaotong Yunnan 657000, China)
出处
《复旦学报（自然科学版）》
CAS
CSCD
北大核心
2019年第2期135-143,共9页
Journal of Fudan University：Natural Science
关键词
细菌耐药性
外排泵
外排泵抑制剂
bacterial drug resistance
efflux pumps
efflux pump inhibitors
