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

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

Author information

1
From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
2
the Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PX, United Kingdom.
3
the Medical Microbiology, Centre for Infection and Immunity, Division of Clinical Sciences, St. George's University of London, London SW17 0RE, United Kingdom.
4
the Centre de Biochimie Structurale, CNRS UMR 5048, 34090 Montpellier, France, INSERM U1054, Universités Montpellier I and II, 34090 Montpellier, France, and.
5
the Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DD, United Kingdom.
6
From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom, gvm4@le.ac.uk.

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

PMID:
25012658
PMCID:
PMC4155686
DOI:
10.1074/jbc.M114.577338
[Indexed for MEDLINE]
Free PMC Article

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