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Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

Turapov, O; Waddell, SJ; Burke, B; Glenn, S; Sarybaeva, AA; Tudo, G; Labesse, G; Young, DI; Young, M; Andrew, PW; et al. Turapov, O; Waddell, SJ; Burke, B; Glenn, S; Sarybaeva, AA; Tudo, G; Labesse, G; Young, DI; Young, M; Andrew, PW; Butcher, PD; Cohen-Gonsaud, M; Mukamolova, GV (2014) Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 58 (5). 2798 - 2806. ISSN 0066-4804 /10.1128/AAC.02774-13
SGUL Authors: Butcher, Philip David

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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
Additional Information: Copyright © 2014 Turapov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.
Keywords: Science & Technology, Life Sciences & Biomedicine, Microbiology, Pharmacology & Pharmacy, MICROBIOLOGY, PHARMACOLOGY & PHARMACY, TRANSCRIPTIONAL REPRESSORS, ANTIBIOTIC TOLERANCE, LATENT TUBERCULOSIS, RESISTANCE, BACTERIA, EFFLUX, GENES, DRUGS, PYRAZINAMIDE, CHEMOTHERAPY, Microbiology, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology And Pharmaceutical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN: 0066-4804
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Dates:
DateEvent
1 May 2014Published
Web of Science ID: WOS:000334364300037
URI: https://openaccess.sgul.ac.uk/id/eprint/107176
Publisher's version: /10.1128/AAC.02774-13

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