MmpL Genes Are Associated with Mycolic Acid Metabolism in Mycobacteria and Corynebacteria

Cristian Varela, D Rittmann, Albel Singh, K Krumbach, K Bhatt, L Eggeling, Gurdyal Besra, Apoorva Bhatt

Research output: Contribution to journalArticle

131 Citations (Scopus)


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 NCgl0228NCgl2769 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.
Original languageEnglish
Pages (from-to)498-506
Number of pages9
JournalChemistry & Biology
Issue number4
Publication statusPublished - 1 Apr 2012


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