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Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

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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 Mukamolova
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Antimicrobial Agents and Chemotherapy

ISSN

1098-6596

Publisher

American Society for Microbiology

Issue

5

Volume

58

Page range

2798-2806

Department affiliated with

  • Global Health and Infection Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2014-05-18

First Open Access (FOA) Date

2014-12-01

First Compliant Deposit (FCD) Date

2014-05-18

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