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

doi:10.1074/jbc.M114.577338

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 journal › Article › peer-review

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 language	English
Pages (from-to)	25241-9
Number of pages	9
Journal	Journal of Biological Chemistry
Volume	289
Issue number	36
Early online date	10 Jul 2014
DOIs	https://doi.org/10.1074/jbc.M114.577338
Publication status	Published - 5 Sep 2014
Externally published	Yes

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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Turapov, O., Waddell, S. J., Burke, B., Glenn, S., Sarybaeva, A. A., Tudo, G., Labesse, G., Young, D. I., Young, M., Andrew, P. W., Butcher, P. D., Cohen-Gonsaud, M., & Mukamolova, G. V. (2014). Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria. Journal of Biological Chemistry, 289(36), 25241-9. https://doi.org/10.1074/jbc.M114.577338

Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria. / Turapov, Obolbek; Waddell, Simon J; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A; Tudo, Griselda; Labesse, Gilles; Young, Danielle I; Young, Michael; Andrew, Peter W; Butcher, Philip D; Cohen-Gonsaud, Martin; Mukamolova, Galina V.

In: Journal of Biological Chemistry, Vol. 289, No. 36, 05.09.2014, p. 25241-9.

Research output: Contribution to journal › Article › peer-review

Turapov, O, Waddell, SJ, Burke, B, Glenn, S, Sarybaeva, AA, Tudo, G, Labesse, G, Young, DI, Young, M, Andrew, PW, Butcher, PD, Cohen-Gonsaud, M & Mukamolova, GV 2014, 'Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria', Journal of Biological Chemistry, vol. 289, no. 36, pp. 25241-9. https://doi.org/10.1074/jbc.M114.577338

Turapov, Obolbek ; Waddell, Simon J ; Burke, Bernard ; Glenn, Sarah ; Sarybaeva, Asel A ; Tudo, Griselda ; Labesse, Gilles ; Young, Danielle I ; Young, Michael ; Andrew, Peter W ; Butcher, Philip D ; Cohen-Gonsaud, Martin ; Mukamolova, Galina V. / Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 36. pp. 25241-9.

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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-Gu{\'e}rin, 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.",

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AU - Burke, Bernard

AU - Glenn, Sarah

AU - Sarybaeva, Asel A

AU - Tudo, Griselda

AU - Labesse, Gilles

AU - Young, Danielle I

AU - Young, Michael

AU - Andrew, Peter W

AU - Butcher, Philip D

AU - Cohen-Gonsaud, Martin

AU - Mukamolova, Galina V

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N2 - 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.

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KW - Binding Sites

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KW - Mycobacterium tuberculosis

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