ArticleNature microbiology2021
Parallel in vivo experimental evolution reveals that increased stress resistance was key for the emergence of persistent tuberculosis bacilli.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Simulating the host niche: balancing complexity and control in the experimental evolution of antibiotic resistance and pathoadaptation.Microbiology (Reading, England) · 2026Review
- Genome graphs reveal the importance of structural variation in Mycobacterium tuberculosis evolution and drug resistance.Nature communications · 2025Article
- Genes required forbioRxiv : the preprint server for biology · 2025Article
- Evolution and emergence of Mycobacterium tuberculosis.FEMS microbiology reviews · 2024Review
- A smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex.Nature communications · 2023Article
- Natural mutations in the sensor kinase of the PhoPR two-component regulatory system modulate virulence of ancestor-like tuberculosis bacilli.PLoS pathogens · 2023Article
- Analysis of Genome-Wide Mutational Dependence in Naturally Evolving Mycobacterium tuberculosis Populations.Molecular biology and evolution · 2023Article
- Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall-targeting antimicrobials.The Journal of biological chemistry · 2022Article
- Triazolopyrimidines Target Aerobic Respiration in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2022Article
- Multiple genetic paths including massive gene amplification allowProceedings of the National Academy of Sciences of the United States of America · 2022Article
- 2021 in review.Nature microbiology · 2021Article
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15 authors.
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Abstract
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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