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 | |
| Publication status | Published - 5 Sep 2014 |
| Externally published | Yes |
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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
Cite this
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
}
TY - JOUR
T1 - Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria
AU - Turapov, Obolbek
AU - Waddell, Simon J
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
N1 - © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2014/9/5
Y1 - 2014/9/5
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.
AB - 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.
KW - Acyl Coenzyme A
KW - Amino Acid Sequence
KW - Bacterial Proteins
KW - Binding Sites
KW - DNA, Bacterial
KW - Fluorescence Polarization
KW - Gene Expression Regulation, Bacterial
KW - Microbial Viability
KW - Molecular Sequence Data
KW - Molecular Structure
KW - Mutation
KW - Mycobacterium
KW - Mycobacterium bovis
KW - Mycobacterium tuberculosis
KW - Oleic Acid
KW - Palmitoyl Coenzyme A
KW - Protein Binding
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Sequence Homology, Amino Acid
KW - Transcriptome
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1074/jbc.M114.577338
DO - 10.1074/jbc.M114.577338
M3 - Article
VL - 289
SP - 25241
EP - 25249
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 36
ER -