Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.
Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.
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DOI：
10.1128/aac.02774-13
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发表时间：
2014-05
影响因子：
4.9
通讯作者：
Mukamolova GV
中科院分区：
文献类型：
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作者：
Turapov O;Waddell SJ;Burke B;Glenn S;Sarybaeva AA;Tudo G;Labesse G;Young DI;Young M;Andrew PW;Butcher PD;Cohen-Gonsaud M;Mukamolova GV
靶向细胞壁生物合成的抗菌剂通常被认为对非复制细菌无活性。矛盾的是，我们发现在非许可生长条件下，牛分枝杆菌卡介苗暴露于这些抗菌剂可提高其存活率。我们确定了由bcg1279 （rv1219c）编码的转录调节因子RaaS（抗菌剂辅助生存调节因子）负责观察到的现象。诱导该转录调节因子导致特异性atp依赖性外排泵的表达减少，促进了分枝杆菌的长期存活，而在体外非允许生长条件下，巨噬细胞或小鼠感染期间，其缺失加速了细菌的死亡。这些发现对设计针对持续性传染病（如结核病）的抗菌药物联合疗法具有启示意义。
Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis.