title: RND transporters protect Corynebacterium glutamicum from antibiotics by assembling the outer membrane.
abstract: Corynebacterium-Mycobacterium-Nocardia (CMN) group are the causative agents of a broad spectrum of diseases in humans. A distinctive feature of these Gram-positive bacteria is the presence of an outer membrane of unique structure and composition. Recently, resistance-nodulation-division (RND) transporters (nicknamed MmpLs, Mycobacterial membrane protein Large) have emerged as major contributors to the biogenesis of the outer membranes in mycobacteria and as promising drug targets. In this study, we investigated the role of RND transporters in the physiology of Corynebacterium glutamicum and analyzed properties of these proteins. Our results show that in contrast to Gram-negative species, in which RND transporters actively extrude antibiotics from cells, in C. glutamicum and relatives these transporters protect cells from antibiotics by playing essential roles in the biogenesis of the low-permeability barrier of the outer membrane. Conditional C. glutamicum mutants lacking RND proteins and with the controlled expression of either NCgl2769 (CmpL1) or NCgl0228 (CmpL4) are hypersusceptible to multiple antibiotics, have growth deficiencies in minimal medium and accumulate intracellularly trehalose monocorynomycolates, free corynomycolates, and the previously uncharacterized corynomycolate-containing lipid. Our results also suggest that similar to other RND transporters, Corynebacterial membrane proteins Large (CmpLs) functions are dependent on a proton-motive force.
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma, 73019.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Shuo
authors.initials: S
authors.lastname: Lu
authors.forename: Juan
authors.initials: J
authors.lastname: Belardinelli
authors.forename: Emilie
authors.initials: E
authors.lastname: Huc-Claustre
authors.forename: Victoria
authors.initials: V
authors.lastname: Jones
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
authors.forename: Helen I
authors.initials: HI
authors.lastname: Zgurskaya
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D048230:Corynebacterium glutamicum / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D055785:Gene Knockdown Techniques; D005798:Genes, Bacterial; D020043:Genes, Essential; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D018892:Proton-Motive Force
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D026901:Membrane Transport Proteins
keywords: Cell envelope; membrane transport; resistance-nodulation-division family