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Antimicrob Agents Chemother. 2014 May;58(5):2798-806. doi: 10.1128/AAC.02774-13. Epub 2014 Mar 3.

Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.

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1
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.

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.

PMID:
24590482
PMCID:
PMC3993263
DOI:
10.1128/AAC.02774-13
[Indexed for MEDLINE]
Free PMC Article
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