摘要
结核病耐药率的攀升是目前全球结核病防控面临的重大挑战。结核分枝杆菌主要通过其基因组中耐药相关基因发生点突变而获得耐药性。由于耐药相关基因通常具有重要的生理功能,其突变往往会导致结核分枝杆菌自身适应性下降,即产生"适应性代价"。然而,耐药结核分枝杆菌可通过进一步积累其他特定突变来回复其适应性,这种能使其适应性上升的突变称为"补偿性突变"。耐药结核分枝杆菌的补偿性进化被认为是耐药结核病广泛传播与流行的生物学基础。近年来,在结核病分子流行病学和基础研究领域,针对耐药结核分枝杆菌的补偿性进化开展了大量研究。本文从结核分枝杆菌的耐药分子机制、耐药突变的适应性代价与补偿性进化,以及补偿性进化如何影响耐药结核病传播等方面,综述耐药结核分枝杆菌补偿性进化的研究进展。
The increasing rate of drug resistance in tuberculosis possesses a great challenge to the global tuberculosis control.The drug resistance in Mycobacterium tuberculosis（M.tuberculosis）is mainly conferred by chromosomal mutations in essential and highly conserved genes,and usually accompanied by a reduction in fitness,namely ＂fitness cost＂.However,this fitness cost can be ameliorated by secondary compensatory mutations which help restore the fitness of drug-resistant strains.The compensatory evolution has been regarded as the biological basis of the extensive spread and high prevalence of drug-resistant M.tuberculosis.Recently,a series of scientific works in the field of molecular epidemiology of tuberculosis and the basic research on the compensatory evolution of drug-resistant M.tuberculosis have been conducted.In this review,we focus on the molecular mechanisms for fitness cost of drug resistance,the compensatory evolution and the potential impacts of these two processes on the transmission of M.tuberculosis.
出处
《微生物与感染》
2017年第6期362-368,共7页
Journal of Microbes and Infections
基金
国家自然科学基金(91631301)
关键词
结核分枝杆菌
耐药突变
适应性代价
补偿性进化
异位显性
Mycobacterium luberculosis
Drug-resistance mutation
Fitness cost
Compensatory evolution
Epistasis
