title: An acyl-CoA synthetase in Mycobacterium tuberculosis involved in triacylglycerol accumulation during dormancy.
abstract: Latent infection with dormant Mycobacterium tuberculosis is one of the major reasons behind the emergence of drug-resistant strains of the pathogen worldwide. In its dormant state, the pathogen accumulates lipid droplets containing triacylglycerol synthesized from fatty acids derived from host lipids. In this study, we show that Rv1206 (FACL6), which is annotated as an acyl-CoA synthetase and resembles eukaryotic fatty acid transport proteins, is able to stimulate fatty acid uptake in E. coli cells. We show that purified FACL6 displays acyl-coenzyme A synthetase activity with a preference towards oleic acid, which is one of the predominant fatty acids in host lipids. Our results indicate that the expression of FACL6 protein in Mycobacterium tuberculosis is significantly increased during in vitro dormancy. The facl6-deficient Mycobacterium tuberculosis mutant displayed a diminished ability to synthesize acyl-coenzyme A in cell-free extracts. Furthermore, during in vitro dormancy, the mutant synthesized lower levels of intracellular triacylglycerol from exogenous fatty acids. Complementation partially restored the lost function. Our results suggest that FACL6 modulates triacylglycerol accumulation as the pathogen enters dormancy by activating fatty acids.
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, 32816, United States of America; Department of Biology, Indiana University-Purdue University Fort Wayne, Fort Wayne, Indiana, 46805, United States of America.
authors.forename: Jaiyanth
authors.initials: J
authors.lastname: Daniel
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, 32816, United States of America.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sirakova
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, 32816, United States of America.
authors.forename: Pappachan
authors.initials: P
authors.lastname: Kolattukudy
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000595:Amino Acid Sequence; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D003001:Cloning, Molecular; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000254:growth & development*; D017386:Sequence Homology, Amino Acid; D014280:Triglycerides / Q000096:biosynthesis*; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D005227:Fatty Acids; D014280:Triglycerides; D003066:Coenzyme A Ligases