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

J Biol Chem. 2014 Sep 5;289(36):25241-9. doi: 10.1074/jbc.M114.577338. Epub 2014 Jul 10.

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.

Keywords: ABC Transporter; Antibiotics; Fatty Acid; Ligand-binding Protein; Mycobacteria; Transcription Repressor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / chemistry
  • Acyl Coenzyme A / metabolism*
  • Amino Acid Sequence
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites / genetics
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism*
  • Fluorescence Polarization
  • Gene Expression Regulation, Bacterial / drug effects
  • Microbial Viability / drug effects
  • Microbial Viability / genetics
  • Molecular Sequence Data
  • Molecular Structure
  • Mutation
  • Mycobacterium / genetics
  • Mycobacterium / metabolism*
  • Mycobacterium bovis / genetics
  • Mycobacterium bovis / metabolism
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism
  • Oleic Acid / pharmacology
  • Palmitoyl Coenzyme A / chemistry
  • Palmitoyl Coenzyme A / metabolism
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Transcriptome / drug effects
  • Transcriptome / genetics

Substances

  • Acyl Coenzyme A
  • Bacterial Proteins
  • DNA, Bacterial
  • oleoyl-coenzyme A
  • Palmitoyl Coenzyme A
  • Oleic Acid