ArticleProceedings of the National Academy of Sciences of the United States of America2016
Temporal and intrinsic factors of rifampicin tolerance in mycobacteria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 54 citations in OpenAlex.
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- Morphological profiling of tubercle bacilli identifies drug pathways of action.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Clinically relevant mutations in mycobacterial LepA cause rifampicin-specific phenotypic resistance.Scientific reports · 2020Article
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6 authors at 3 institutions in 2 countries.
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Abstract
Mycobacteria grow and divide asymmetrically, creating variability in growth pole age, growth properties, and antibiotic susceptibilities. Here, we investigate the importance of growth pole age and other growth properties in determining the spectrum of responses of Mycobacterium smegmatis to challenge with rifampicin. We used a combination of live-cell microscopy and modeling to prospectively identify subpopulations with altered rifampicin susceptibility. We found two subpopulations that had increased susceptibility. At the initiation of treatment, susceptible cells were either small and at early stages of the cell cycle, or large and in later stages of their cell cycle. In contrast to this temporal window of susceptibility, tolerance was associated with factors inherited at division: long birth length and mature growth poles. Thus, rifampicin response is complex and due to a combination of differences established from both asymmetric division and the timing of treatment relative to cell birth.
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