title: A novel marRAB operon contributes to the rifampicin resistance in Mycobacterium smegmatis.
abstract: The multiple-antibiotic resistance regulator (MarR) plays an important role in modulating bacterial antibiotic resistance. However, the regulatory model of the marRAB operon in mycobacteria remains to be characterized. Here we report that a MarR, encoded by Ms6508, and its marRAB operon specifically contribute to rifampicin (RIF) resistance in Mycobacterium smegmatis. We show that the MarR recognizes a conserved 21-bp palindromic motif and negatively regulates the expression of two ABC transporters in the operon, encoded by Ms6509-6510. Unlike other known drug efflux pumps, overexpression of these two ABC transporters unexpectedly increased RIF sensitivity and deletion of these two genes increased mycobacterial resistance to the antibiotic. No change can be detected for the sensitivity of recombinant mycobacterial strains to three other anti-TB drugs. Furthermore, HPLC experiments suggested that Ms6509-Ms6510 could pump RIF into the mycobacterial cells. These findings indicated that the mycobacterial MarR functions as a repressor and constitutively inhibits the expression of the marRAB operon, which specifically contributes to RIF resistance in M. smegmatis. Therefore, our data suggest a new regulatory mechanism of RIF resistance and also provide the new insight into the regulatory model of a marRAB operon in mycobacteria.
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Long
authors.initials: L
authors.lastname: Gao
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Jiaoling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Li
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Gao
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Zheng-Guo
authors.initials: ZG
authors.lastname: He
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000235:genetics*; D009876:Operon / Q000235:genetics*; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D012293:Rifampin