Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Turapov, Obolbek, Waddell, Simon J, Burke, Bernard, Glenn, Sarah, Sarybaeva, Asel A, Tudo, Griselda, Labesse, Gilles, Young, Danielle I, Young, Michael, Andrew, Peter W, Butcher, Philip D, Cohen-Gonsaud, Martin and Mukamolova, Galina V (2014) Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions. Antimicrobial Agents and Chemotherapy, 58 (5). pp. 2798-2806. ISSN 1098-6596

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Abstract

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Subjects: Q Science > QR Microbiology
Q Science > QR Microbiology > QR0075 Bacteria
Depositing User: Simon Waddell
Date Deposited: 18 May 2014 09:57
Last Modified: 03 Aug 2017 17:22
URI: http://sro.sussex.ac.uk/id/eprint/48722

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