title: Characterization of a two-gene operon epeRA involved in multidrug resistance in Streptomyces clavuligerus.
abstract: Two genes, epeR and epeA, are located downstream of argH in the Streptomyces clavuligerus genome. EpeR belongs to the TetR family of transcriptional regulators. It is homologous to PqrA of Streptomyces coelicolor (74.3% identity) and to NfxB of Pseudomonas aeruginosa (30.9% identity). EpeA encodes a protein with 14 transmembrane spanning domains (TMS) of the major facilitator superfamily. It shares 68.9% identity to PqrB of S. coelicolor and 46.5% identity to LfrA, conferring resistance to fluoroquinolones in Mycobacterium smegmatis. Disruption of epeR results in a S. clavuligerus epeR::aph mutant which shows increased resistance to ethidium bromide and proflavine (16- and 32-fold higher than the wild type). Taking into consideration the sensitivity to drugs of different transformants carrying functional copies of either epeR or epeA, it might be concluded that both genes appear to be co-transcribed, with epeR encoding a regulatory protein which controls the expression of epeA.
authors.affiliation: Area de Microbiología, Facultad de Ciencias Biológicas y Ambientales, Universidad de León, 24071 León, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-García
authors.forename: Irene
authors.initials: I
authors.lastname: Santamarta
authors.forename: Rosario
authors.initials: R
authors.lastname: Pérez-Redondo
authors.forename: Juan F
authors.initials: JF
authors.lastname: Martín
authors.forename: Paloma
authors.initials: P
authors.lastname: Liras
mesh_terms: D000595:Amino Acid Sequence; D019818:Clavulanic Acid / Q000096:biosynthesis; D024901:Drug Resistance, Multiple, Bacterial; D004996:Ethidium / Q000494:pharmacology; D005798:Genes, Bacterial; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D050296:Microbial Viability; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon; D011370:Proflavine / Q000494:pharmacology; D013302:Streptomyces / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D019818:Clavulanic Acid; D011370:Proflavine; D004996:Ethidium