Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis
Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis
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DOI：
10.1128/aac.43.8.1866
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发表时间：
1999-08-01
影响因子：
4.9
通讯作者：
Gillespie, SH
中科院分区：
文献类型：
--
作者：
Billington, OJ;McHugh, TD;Gillespie, SH
耐药结核分枝杆菌是对公众健康的主要威胁。在临床实践中，已经描述了RNA聚合酶β亚基（由rpoB编码）的短序列中有限数量的耐药突变。体外诱导结核分枝杆菌H37Rv（ATCC 9360）对利福平产生自发耐药，通过PCR-单链构象多态性分析只能检测到三种耐药模式。序列分析显示，Ser(531)-->Leu 出现最频繁，其次是 His(526)-->Arg，然后是 His(526)-->Tyr 或 His(526)-->ASP。除一种突变基因型外，所有突变基因型的相对达尔文适应性均低于易感亲本，对于这些突变，适应性和临床分离率之间存在显着相关性（回归分析 P = 0.026）。一些突变体的适应度缺陷很小，这表明自发恢复易感性的可能性很小。
Drug-resistant Mycobacterium tuberculosis is a major threat to public health. In clinical practice, a limited number of resistance mutations in a short sequence of the beta subunit of RNA polymerase (encoded by rpoB) have been described. Spontaneous resistance to rifampin was induced in vitro in M. tuberculosis H37Rv (ATCC 9360), Only three resistance patterns could be detected by PCR-single-strand conformation polymorphism analysis. Sequence analysis revealed that Ser(531)-->Leu arose most frequently, followed by His(526)-->Arg and then either His(526)-->Tyr or His(526)-->ASP The relative Darwinian fitness of all but one of the mutant genotypes was less than that of the susceptible parent and, for these mutations, there was a significant correlation between fitness and clinical isolation rate (regression analysis P = 0.026). The fitness deficit in some mutants was small, suggesting that there is little likelihood of a spontaneous reversion to susceptibility.