Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria

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

1 Citation (Scopus)

Abstract

We have recently shown that RaaS (regulator of antimicrobial-assisted survival), encoded by Rv1219c in Mycobacterium tuberculosis and by bcg_1279c in Mycobacterium bovis bacillus Calmette-Guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. Here, we demonstrate that long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, palmitoyl-CoA) modulate RaaS binding to DNA and expression of the downstream genes that encode ATP-dependent efflux pumps. Moreover, exogenously added oleic acid influences RaaS-mediated mycobacterial improvement of survival and expression of the RaaS regulon. Our data suggest that long chain acyl-CoA derivatives serve as biological indicators of the bacterial metabolic state. Dysregulation of efflux pumps can be used to eliminate non-growing mycobacteria.

Original languageEnglish
Pages (from-to)25241-9
Number of pages9
JournalJournal of Biological Chemistry
Volume289
Issue number36
Early online date10 Jul 2014
DOIs
Publication statusPublished - 5 Sep 2014
Externally publishedYes

Keywords

  • Acyl Coenzyme A
  • Amino Acid Sequence
  • Bacterial Proteins
  • Binding Sites
  • DNA, Bacterial
  • Fluorescence Polarization
  • Gene Expression Regulation, Bacterial
  • Microbial Viability
  • Molecular Sequence Data
  • Molecular Structure
  • Mutation
  • Mycobacterium
  • Mycobacterium bovis
  • Mycobacterium tuberculosis
  • Oleic Acid
  • Palmitoyl Coenzyme A
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Transcriptome
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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