小柯机器人

美国哈佛大学Sarah M. Fortune研究小组发现，结核病治疗失败与抗生素恢复力的演变有关。这一研究成果发表在2022年12月9日出版的国际学术期刊《科学》上。

通过对51229个结核分枝杆菌（Mtb）临床分离物的基因组分析，研究人员发现了一个重要的转录调节因子Rv1830，被称为resR。这代表了恢复力调节因子，是正向（适应性）选择的频繁目标。resR突变体不显示典型的抗药性或耐药性，而是缩短抗生素后效应，意味着它们使Mtb在药物暴露后比野生型菌株更快地恢复生长。

研究人员把这种表型称为抗生素恢复力。ResR与其他控制细胞生长和分裂的转录因子共同作用于一个调控级联，这些转录因子在Mtb的临床分离株中也处于正选择状态。这些基因的突变与治疗失败和获得典型的耐药性有关。

据悉，抗生素的广泛使用使细菌病原体面临着演化出新生存机制的巨大压力。

附：英文原文

Title: Tuberculosis treatment failure associated with evolution of antibiotic resilience

Author: 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. Fortune

Issue&Volume: 2022-12-09

Abstract: 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.

DOI: abq2787

Source: https://www.science.org/doi/10.1126/science.abq2787