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 |
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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 Sept 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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Bernard Burke
- Centre for Health and Life Sciences - Associate Professor Research
Person: Teaching and Research