title: Characterization of the MSMEG_2631 gene (mmp) encoding a multidrug and toxic compound extrusion (MATE) family protein in Mycobacterium smegmatis and exploration of its polyspecific nature using biolog phenotype microarray.
abstract: In Mycobacterium, multidrug efflux pumps can be associated with intrinsic drug resistance. Comparison of putative mycobacterial transport genes revealed a single annotated open reading frame (ORF) for a multidrug and toxic compound extrusion (MATE) family efflux pump in all sequenced mycobacteria except Mycobacterium leprae. Since MATE efflux pumps function as multidrug efflux pumps by conferring resistance to structurally diverse antibiotics and DNA-damaging chemicals, we studied this gene (MSMEG_2631) in M. smegmatis mc(2)155 and determined that it encodes a MATE efflux system that contributes to intrinsic resistance of Mycobacterium. We propose that the MSMEG_2631 gene be named mmp, for mycobacterial MATE protein. Biolog Phenotype MicroArray data indicated that mmp deletion increased susceptibility for phleomycin, bleomycin, capreomycin, amikacin, kanamycin, cetylpyridinium chloride, and several sulfa drugs. MSMEG_2619 (efpA) and MSMEG_3563 mask the effect of mmp deletion due to overlapping efflux capabilities. We present evidence that mmp is a part of an MSMEG_2626-2628-2629-2630-2631 operon regulated by a strong constitutive promoter, initiated from a single transcription start site. All together, our results show that M. smegmatis constitutively encodes an Na(+)-dependent MATE multidrug efflux pump from mmp in an operon with putative genes encoding proteins for apparently unrelated functions.
authors.affiliation: Department of Pharmaceutical Sciences, Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy, Kingsville, TX, USA.
authors.forename: Mukti Nath
authors.initials: MN
authors.lastname: Mishra
authors.forename: Lacy
authors.initials: L
authors.lastname: Daniels
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D024901:Drug Resistance, Multiple, Bacterial; D017353:Gene Deletion; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism*; D009876:Operon; D010641:Phenotype; D011401:Promoter Regions, Genetic; D013379:Substrate Specificity; D024363:Transcription Initiation Site
chemical_list: D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins