宋婧 车南颖

[摘要] 本文综述了结核分枝杆菌（MTB）的耐药机制和检测方法。耐药机制分为细胞壁渗透性降低及外排泵作用的固有性耐药机制和靶基因突变的获得性耐药机制。隨着分子生物学技术的发展，药物作用的靶基因突变被认为是MTB耐药的主要机制。耐药的检测方法主要为表型药敏检测和分子药敏检测。表型检测方法为金标准，但检测周期较长，而基因突变检测可以在几个小时内完成，在结核病的诊断中有更好的应用前景。本文对MTB的耐药机制和检测方法进行综述，以期为开发快速分子诊断工具和抗结核新药的研发提供参考或借鉴。

[关键词] 结核分枝杆菌；耐药；检测方法

[中图分类号] R378.91 [文献标识码] A [文章编号] 1673-7210（2018）10（b）-0029-06

[Abstract] This article reviews the mechanism and detection methods of drug resistance in Mycobacterium tuberculosis（MTB）. The mechanism of drug resistance is divided into intrinsic resistance mechanism of cell wall permeability reduction and efflux pump action and acquired resistance mechanism of target gene mutation. With the development of molecular biology techniques， mutations in target genes are considered to be the main mechanism of drug resistance for MTB. The main detection methods for drug resistance are phenotypic susceptibility testing and molecular susceptibility testing. The phenotypic assay method is used as the golden standard， but the detection period is long， while gene mutation detection can be completed within a few hours， so there is a better application prospect in the diagnosis of tuberculosis. In this paper， the mechanism and detection methods of drug resistance in MTB are reviewed in order to provide some reference for the development of rapid molecular diagnostic tools and anti-tuberculosis drugs.

[Key words] Mycobacterium tuberculosis； Drug resistance； Detection method

结核病（tuberculosis，TB）是由结核分枝杆菌（Mycobacterium tuberculosis，MTB）感染所致的慢性传染病。尽管近年来TB的防治取得了进展，但其仍然是全球十大死因之一。根据2017年WHO最新报告，2016年全球估计有1040万TB新发病例[1]。中国TB新发病例在90万左右，新发耐药TB患者约5.8万人，且大部分患者未被发现或未接受治疗，我国TB的形势依然严峻，而MTB的耐药是治疗TB亟待解决的难题之一。目前部分阐明的MTB的耐药机制分为固有性耐药机制和获得性耐药机制，且药物作用的靶基因突变的获得性分子耐药机制是MTB耐药的主要机制[2]。MTB耐药性的检测方法分为表型药敏试验和耐药基因突变检测两种方法。本文对MTB耐药机制和检测方法进行了综述与展望。

1 MTB耐药机制

1.1 固有性耐药机制

1.1.1 MTB细胞壁渗透性障碍 细胞壁渗透性障碍，是MTB对常见的非抗结核抗生素产生耐药的原因之一。……