Antimicrob._Agents_Chemother.-2014-Turapov-2798-806.pdf (975.33 kB)
Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions
journal contribution
posted on 2023-06-08, 17:20 authored by Obolbek Turapov, Simon WaddellSimon Waddell, Bernard Burke, Sarah Glenn, Asel A Sarybaeva, Griselda Tudo, Gilles Labesse, Danielle I Young, Michael Young, Peter W Andrew, Philip D Butcher, Martin Cohen-Gonsaud, Galina V MukamolovaAntimicrobials 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.
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Publication status
- Published
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- Published version
Journal
Antimicrobial Agents and ChemotherapyISSN
1098-6596Publisher
American Society for MicrobiologyExternal DOI
Issue
5Volume
58Page range
2798-2806Department affiliated with
- Global Health and Infection Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2014-05-18First Open Access (FOA) Date
2014-12-01First Compliant Deposit (FCD) Date
2014-05-18Usage metrics
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