title: MmpL genes are associated with mycolic acid metabolism in mycobacteria and corynebacteria.
abstract: 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.
authors.affiliation: School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
authors.forename: Cristian
authors.initials: C
authors.lastname: Varela
authors.forename: Doris
authors.initials: D
authors.lastname: Rittmann
authors.forename: Albel
authors.initials: A
authors.lastname: Singh
authors.forename: Karin
authors.initials: K
authors.lastname: Krumbach
authors.forename: Kiranmai
authors.initials: K
authors.lastname: Bhatt
authors.forename: Lothar
authors.initials: L
authors.lastname: Eggeling
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Apoorva
authors.initials: A
authors.lastname: Bhatt
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003352:Corynebacterium / Q000378:metabolism*; D055786:Gene Knockout Techniques; D009161:Mycobacterium / Q000187:drug effects / Q000378:metabolism*; D009171:Mycolic Acids / Q000378:metabolism*
chemical_list: D000081:Acetamides; D001426:Bacterial Proteins; D009171:Mycolic Acids; C030686:acetamide