title: Indole induces the expression of multidrug exporter genes in Escherichia coli.
abstract: Our comprehensive expression cloning studies previously revealed that 20 intrinsic xenobiotic exporter systems are encoded in the Escherichia coli chromosome, but most of them are not expressed under normal conditions. In this study, we investigated the compounds that induce the expression of these xenobiotic exporter genes, and found that indole induces a variety of xenobiotic exporter genes including acrD, acrE, cusB, emrK, mdtA, mdtE and yceL. Indole treatment of E. coli cells confers rhodamine 6G and SDS resistance through the induction of mdtEF and acrD gene expression respectively. The induction of mdtE by indole is independent of the EvgSA two-component signal transduction system that regulates the mdtE gene, but mediated by GadX. On the other hand, the induction of acrD and mdtA was mediated by BaeSR and CpxAR, two-component systems. Interestingly, CpxAR system-mediated induction required intrinsic baeSR genes, whereas BaeSR-mediated induction was observed in the cpxAR gene-deletion mutant. BaeR and CpxR directly bound to different sequences of the acrD and mdtA promoter regions. These observations indicate that BaeR is a primary regulator, and CpxR enhances the effect of BaeR.
authors.affiliation: Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Hidetada
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Inazumi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Masaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirata
authors.forename: Akihito
authors.initials: A
authors.lastname: Yamaguchi
mesh_terms: D001483:Base Sequence; D002876:Chromosomes, Bacterial / Q000235:genetics; D018983:DNA Footprinting; D003850:Deoxyribonuclease I; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015262:Xenobiotics / Q000493:pharmacokinetics
chemical_list: D003850:Deoxyribonuclease I; D029968:Escherichia coli Proteins; D007211:Indoles; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015262:Xenobiotics