结核分枝杆菌对抗结核药物耐受机制的研究进展

Research progress in the mechanism of drug resistance in Mycobacterium tuberculosis

结核分枝杆菌（Mtb）耐药是目前结核病治疗中亟待解决的难题之一。近20年来已部分阐明了Mtb的耐药分子机制，并建立了一些常见抗结核药物的分子药物敏感性试验方法并在临床应用，以指导化疗。笔者简要地概述了Mtb对抗结核药物耐受的4种分子机制及其新进展：（1）Mtb耐药相关基因突变；（2）Mtb外排泵基因过表达；（3）Mtb细胞壁渗透性的改变；（4）Mtb双组分系统表达显著升高。作者并指出了存在的问题及未来研究的方向，为耐药检测新方法的建立及抗结核新药的研发奠定基础。

Mycobacterium tuberculosis （Mtb） resistance to drugs is one of the difficult problems to be solved in the treatment of tuberculosis （TB）. In the last 20 years, some molecular mechanisms of drug resistance in Mtb have been clarified, and some molecular drug susceptibility test methods for the common anti-TB drugs have been estab- lished and used to direct the chemotherapy in the clinic. This paper briefly overviews four molecular mechanisms of drug resistance in Mtb and its new progress： （1） The mutations of Mtb drug-resistance associated genes; （2） The over-expression of Mtb efflux pump genes; （3） The change of Mtb cell wall permeability; （4） The high expression of Mtb two component system. We also point out the existing problems and future research direction, which will lay the foundation for developing new detection methods of Mtb drug resistance and studying new anti-TB drugs.