Pu, Yingying and Zhao, Zhilun and Li, Yingxing and Zou, Jin and Ma, Qi and Zhao, Yanna and Ke, Yuehua and Zhu, Yun and Chen, Huiyi and Baker, Matthew A B and Ge, Hao and Sun, Yujie and Xie, Xiaoliang Sunney and Bai, Fan (2016) Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells. Molecular Cell, 62 (2). pp.284-94. ISSN 1097-4164 (Gold OA)
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Abstract
Natural variations in gene expression provide a mechanism for multiple phenotypes to arise in an isogenic bacterial population. In particular, a sub-group termed persisters show high tolerance to antibiotics. Previously, their formation has been attributed to cell dormancy. Here we demonstrate that bacterial persisters, under β-lactam antibiotic treatment, show less cytoplasmic drug accumulation as a result of enhanced efflux activity. Consistently, a number of multi-drug efflux genes, particularly the central component TolC, show higher expression in persisters. Time-lapse imaging and mutagenesis studies further establish a positive correlation between tolC expression and bacterial persistence. The key role of efflux systems, among multiple biological pathways involved in persister formation, indicates that persisters implement a positive defense against antibiotics prior to a passive defense via dormancy. Finally, efflux inhibitors and antibiotics together effectively attenuate persister formation, suggesting a combination strategy to target drug tolerance.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 27 Apr 2016 22:59 |
| Last Modified: | 27 Apr 2016 23:16 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/422 |
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