title: Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria.
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.
authors.affiliation: From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Obolbek
authors.initials: O
authors.lastname: Turapov
authors.affiliation: the Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PX, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Waddell
authors.affiliation: From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Bernard
authors.initials: B
authors.lastname: Burke
authors.affiliation: From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Glenn
authors.affiliation: From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Asel A
authors.initials: AA
authors.lastname: Sarybaeva
authors.affiliation: the Medical Microbiology, Centre for Infection and Immunity, Division of Clinical Sciences, St. George's University of London, London SW17 0RE, United Kingdom.
authors.forename: Griselda
authors.initials: G
authors.lastname: Tudo
authors.affiliation: the Centre de Biochimie Structurale, CNRS UMR 5048, 34090 Montpellier, France, INSERM U1054, Universités Montpellier I and II, 34090 Montpellier, France, and.
authors.forename: Gilles
authors.initials: G
authors.lastname: Labesse
authors.affiliation: the Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DD, United Kingdom.
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Young
authors.affiliation: the Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DD, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Young
authors.affiliation: From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.affiliation: the Medical Microbiology, Centre for Infection and Immunity, Division of Clinical Sciences, St. George's University of London, London SW17 0RE, United Kingdom.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Butcher
authors.affiliation: the Centre de Biochimie Structurale, CNRS UMR 5048, 34090 Montpellier, France, INSERM U1054, Universités Montpellier I and II, 34090 Montpellier, France, and.
authors.forename: Martin
authors.initials: M
authors.lastname: Cohen-Gonsaud
authors.affiliation: From the Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom, gvm4@le.ac.uk.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Mukamolova
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D005454:Fluorescence Polarization; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D009161:Mycobacterium / Q000235:genetics / Q000378:metabolism*; D009163:Mycobacterium bovis / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D010171:Palmitoyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C017585:oleoyl-coenzyme A; D010171:Palmitoyl Coenzyme A; D019301:Oleic Acid
keywords: ABC Transporter; Antibiotics; Fatty Acid; Ligand-binding Protein; Mycobacteria; Transcription Repressor