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|Title:||Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.|
Waddell, S. J.
Sarybaeva, Asel A.
Young, D. I.
Andrew, Peter W.
Butcher, P. D.
Mukamolova, Galina V.
|Publisher:||American Society for Microbiology|
|Citation:||Antimicrobial Agents and Chemotherapy, 2014, 58 (5), pp. 2798-2806|
|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.|
|Rights:||Copyright © 2014 Turapov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license. http://creativecommons.org/licenses/by/3.0/ (CC BY 3.0)|
|Description:||PMCID: PMC3993263 Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.02774-13.|
|Appears in Collections:||Published Articles, Dept. of Infection, Immunity and Inflammation|
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