结核分枝杆菌
生物
抗药性
肺结核
抗生素耐药性
遗传学
微生物学
突变
分枝杆菌
抗生素
遗传适应性
细菌
基因
医学
病理
作者
Sebastian M. Gygli,Sònia Borrell,Andrej Trauner,Sébastien Gagneux
出处
期刊:Fems Microbiology Reviews
[Oxford University Press]
日期:2017-03-25
卷期号:41 (3): 354-373
被引量:265
标识
DOI:10.1093/femsre/fux011
摘要
Antibiotic-resistant Mycobacterium tuberculosis strains are threatening progress in containing the global tuberculosis epidemic. Mycobacterium tuberculosis is intrinsically resistant to many antibiotics, limiting the number of compounds available for treatment. This intrinsic resistance is due to a number of mechanisms including a thick, waxy, hydrophobic cell envelope and the presence of drug degrading and modifying enzymes. Resistance to the drugs which are active against M. tuberculosis is, in the absence of horizontally transferred resistance determinants, conferred by chromosomal mutations. These chromosomal mutations may confer drug resistance via modification or overexpression of the drug target, as well as by prevention of prodrug activation. Drug resistance mutations may have pleiotropic effects leading to a reduction in the bacterium's fitness, quantifiable e.g. by a reduction in the in vitro growth rate. Secondary so-called compensatory mutations, not involved in conferring resistance, can ameliorate the fitness cost by interacting epistatically with the resistance mutation. Although the genetic diversity of M. tuberculosis is low compared to other pathogenic bacteria, the strain genetic background has been demonstrated to influence multiple aspects in the evolution of drug resistance. The rate of resistance evolution and the fitness costs of drug resistance mutations may vary as a function of the genetic background.
科研通智能强力驱动
Strongly Powered by AbleSci AI