Temporal and intrinsic factors of rifampicin tolerance in mycobacteria

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 challeng...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-07, Vol.113 (29), p.8302-8307
Main Authors: Richardson, Kirill, Bennion, Owen T., Tan, Shumin, Hoang, Anh N., Cokol, Murat, Aldridge, Bree B.
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antibiotics
Bacteria
Biological Sciences
Cell cycle
Cell growth
Drug Resistance, Bacterial - physiology
Microscopy
Mycobacterium smegmatis
Mycobacterium smegmatis - drug effects
Mycobacterium smegmatis - growth & development
Rifampin - pharmacology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1600372113