Temporal and intrinsic factors of rifampicin tolerance in mycobacteria

Richardson, Kirill and Bennion, Owen T. and Tan, Shumin and Hoang, Anh N. and Çokol, Murat and Aldridge, Bree B. (2016) Temporal and intrinsic factors of rifampicin tolerance in mycobacteria. Proceedings of the National Academy of Sciences of the United States of America, 113 (29). pp. 8302-8307. ISSN 0027-8424

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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.
Item Type: Article
Uncontrolled Keywords: antibiotic susceptibility; single cell; mathematical modeling; mycobacteria; cell biology
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Murat Çokol
Date Deposited: 08 Sep 2016 12:07
Last Modified: 08 Sep 2016 12:07
URI: https://research.sabanciuniv.edu/id/eprint/29600

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