Science:结核病治疗失败与抗生素耐药性的演变相关
Tuberculosis treatment failure associated with evolution of antibiotic resilience
作者:Qingyun Liu, Junhao Zhu, Charles L. Dulberger, Sydney Stanley, Sean Wilson, Eun Seon Chung, Xin Wang, Peter Culviner, Yue J. Liu, Nathan D. Hicks, Gregory H. Babunovic, Samantha R. Giffen, Bree B. Aldridge, Ethan C. Garner, Eric J. Rubin, Michael C. Chao, Sarah M.
Science:2022/12/09
The widespread use of antibiotics has placed bacterial pathogens under intense pressure to evolve new survival mechanisms. Genomic analysis of 51,229 Mycobacterium tuberculosis (Mtb) clinical isolates has identified an essential transcriptional regulator, Rv1830, herein called resR for resilience regulator, as a frequent target of positive (adaptive) selection. resR mutants do not show canonical drug resistance or drug tolerance but instead shorten the post-antibiotic effect, meaning that they enable Mtb to resume growth after drug exposure substantially faster than wild-type strains. We refer to this phenotype as antibiotic resilience. ResR acts in a regulatory cascade with other transcription factors controlling cell growth and division, which are also under positive selection in clinical isolates of Mtb. Mutations of these genes are associated with treatment failure and the acquisition of canonical drug resistance.
抗生素的广泛使用给细菌病原体带来巨大压力促进其演化出全新的生存机制。本研究对51229份结核病(Mtb)临床分离株展开基因组分析,识别出一个关键的转录调控因子Rv1830,是正向选择(适应性选择)的常见靶点,其突变没有表现出经典的药物抗性或者耐药性,但缩短了抗生素使用后效果,表明它们帮助Mtb在接触药物后以更快的速度恢复生长。结果揭示了结核病治疗失败与常规药物耐药性相关的调控因子及其突变。
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