Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Obolbek Turapov, Simon J 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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2798-806
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume58
Issue number5
Early online date3 Mar 2014
DOIs
Publication statusPublished - May 2014

Keywords

  • Animals
  • Anti-Infective Agents
  • Cell Line
  • Electrophoretic Mobility Shift Assay
  • Fluorescence Polarization
  • Humans
  • Mice
  • Mycobacterium bovis
  • Mycobacterium tuberculosis
  • Journal Article
  • Research Support, Non-U.S. Gov't

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