生物
互补
结核分枝杆菌
病菌
突变体
肺结核
实验进化
遗传学
抗药性
效应器
表型
微生物学
抗生素耐药性
杆菌
毒力
作者
Aideen C. Allen,Wladimir Malaga,Cyril Gaudin,Arnaud Volle,Flavie Moreau,Ali Hassan,Catherine Astarie-Dequeker,Antonio Peixoto,Rudy Antoine,Alexandre Pawlik,Wafa Frigui,Céline Berrone,Roland Brosch,Philip Supply,Christophe Guilhot
出处
期刊:Nature microbiology
日期:2021-07-22
卷期号:6 (8): 1082-1093
被引量:7
标识
DOI:10.1038/s41564-021-00938-4
摘要
Pathogenomic evidence suggests that Mycobacterium tuberculosis (MTB) evolved from an environmental ancestor similar to Mycobacterium canettii, a rare human pathogen. Although the adaptations responsible for this transition are poorly characterized, the ability to persist in humans seems to be important. We set out to identify the adaptations contributing to the evolution of persistence in MTB. We performed an experimental evolution of eight M. canettii populations in mice; four populations were derived from the isolate STB-K (phylogenomically furthest from MTB) and four from STB-D (closest to MTB), which were monitored for 15 and 6 cycles, respectively. We selected M. canettii mutants with enhanced persistence in vivo compared with the parental strains, which were phenotypically closer to MTB. Genome sequencing of 140 mutants and complementation analysis revealed that mutations in two loci were responsible for enhanced persistence. Most of the tested mutants were more resistant than their parental strains to nitric oxide, an important effector of immunity. Modern MTB were similarly more resistant to nitric oxide than M. canettii. Our findings demonstrate phenotypic convergence during experimental evolution of M. canettii, which mirrors natural evolution of MTB. Furthermore, they indicate that the ability to withstand host-induced stresses was key for the emergence of persistent MTB.
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