title: Overexpression of vmeTUV encoding a multidrug efflux transporter of Vibrio parahaemolyticus causes bile acid resistance.
abstract: We isolated deoxycholate-resistant mutants from Vibrio parahaemolyticus RTM34, which lacks four multidrug efflux transporters belonging to the resistance nodulation cell division (RND) family. RTM34 showed sensitivity to many antimicrobial agents such as cholate and deoxycholate. Deoxycholate-resistant mutants from RTM34 have elevated resistance to not only deoxycholate, but also antibiotics, disinfectants, and dyes. RT-PCR analysis revealed that the expression of vmeV, which encodes an RND-type multidrug efflux transporter, was higher in deoxycholate-resistant mutants than in parental strain RTM34. VPA0806, designated as vdeR, was located upstream of the vmeTUV operon, was oriented in the opposite direction of this operon, and encoded a putative TetR family transcriptional regulator. We determined the nucleotide sequences of vdeR and the vmeT promoter region in the genomes of deoxycholate-resistant mutants. A point mutation was identified in vdeR of seven deoxycholate-resistant mutants and a deletion mutation was identified in vdeR of one deoxycholate-resistant mutant. Since most mutations cause a frame shift mutation and premature stop codon, the function of VdeR is thought to be lost in these mutants. Taken together, the results of the present study indicate that deoxycholate resistance in these mutants was due to the overexpression of vmeTUV caused by a loss in the repression by VdeR.
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: t-matsuo@kph.bunri-u.ac.jp.
authors.forename: Taira
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: wogawa@pharm.okayama-u.ac.jp.
authors.forename: Wakano
authors.initials: W
authors.lastname: Ogawa
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: ttsuchi@fc.ritsumei.ac.jp.
authors.forename: Tomofusa
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: tkuroda@cc.okayama-u.ac.jp.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kuroda
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001647:Bile Acids and Salts / Q000737:chemistry*; D001665:Binding Sites; D003062:Codon; D003840:Deoxycholic Acid / Q000737:chemistry*; D024901:Drug Resistance, Multiple, Bacterial; D017353:Gene Deletion; D044404:Genomic Islands; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014736:Vibrio parahaemolyticus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D003062:Codon; D003840:Deoxycholic Acid
keywords: Deoxycholate resistance; Gene repression; RND-type multidrug efflux transporter