1. MmpL Genes Are Associated with Mycolic Acid Metabolism in Mycobacteria and Corynebacteria
- Author
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Doris Rittmann, Lothar Eggeling, Albel Singh, Gurdyal S. Besra, Kiranmai Bhatt, Karin Krumbach, Cristian Varela, and Apoorva Bhatt
- Subjects
Clinical Biochemistry ,Corynebacterium ,Biochemistry ,Article ,Microbiology ,Mycolic acid ,Corynebacterium glutamicum ,Mycobacterium ,Cell wall ,03 medical and health sciences ,chemistry.chemical_compound ,Gene Knockout Techniques ,Glycolipid ,Bacterial Proteins ,Drug Discovery ,Acetamides ,Molecular Biology ,030304 developmental biology ,Pharmacology ,chemistry.chemical_classification ,0303 health sciences ,biology ,030306 microbiology ,Mycobacterium smegmatis ,General Medicine ,biology.organism_classification ,3. Good health ,Trehalose dimycolate ,chemistry ,Mycolic Acids ,Molecular Medicine - Abstract
Summary Mycolic acids are vital components of the cell wall of the tubercle bacillus Mycobacterium tuberculosis and are required for viability and virulence. While mycolic acid biosynthesis is studied extensively, components involved in mycolate transport remain unidentified. We investigated the role of large membrane proteins encoded by mmpL genes in mycolic acid transport in mycobacteria and the related corynebacteria. MmpL3 was found to be essential in mycobacteria and conditional depletion of MmpL3 in Mycobacterium smegmatis resulted in loss of cell wall mycolylation, and of the cell wall-associated glycolipid, trehalose dimycolate. In parallel, an accumulation of trehalose monomycolate (TMM) was observed, suggesting that mycolic acids were transported as TMM. In contrast to mycobacteria, we found redundancy in the role of two mmpL genes, in Corynebacterium glutamicum; a complete loss of trehalose-associated and cell wall bound corynomycolates was observed in an NCgl0228-NCgl2769 double mutant, but not in individual single mutants. Our studies highlight the role of mmpL genes in mycolic acid metabolism and identify potential new targets for anti-TB drug development., Highlights ► MmpL3 is an essential gene in mycobacteria ► MmpL3 is involved in mycolic acid transport in mycobacteria ► Two mmpL genes are involved in corynomycolate metabolism in corynebacteria
- Published
- 2012