title: Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat.
abstract: Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these, AcrAB is constitutively expressed and is the most efficient, playing a role in both drug resistance and virulence. The acrAB locus is induced by indole, Escherichia coli-conditioned medium, and bile salts. This induction is dependent on RamA through the binding sequence in the upstream region of acrA that binds RamA. In the present study, we made a detailed investigation of the ramA and acrAB induction mechanisms in Salmonella in response to indole, a biological oxidant for bacteria. We found that acrAB and ramA induction in response to indole is dependent on RamR. However, the cysteine residues of RamR do not play a role in the induction of ramA in response to indole, and the oxidative effect of indole is therefore not related to ramA induction via RamR. Furthermore, we showed that paraquat, a superoxide generator, induces acrAB but not ramA. We further discovered that the mechanism of acrAB induction in response to paraquat is dependent on SoxS. The data indicate that there are at least two independent induction pathways for acrAB in response to extracellular signals such as indole and paraquat. We propose that Salmonella utilizes these regulators for acrAB induction in response to extracellular signals in order to adapt itself to environmental conditions.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.|Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.|Laboratory of Microbiology and Infectious Diseases, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nikaido
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.|Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.|Laboratory of Microbiology and Infectious Diseases, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Ikue
authors.initials: I
authors.lastname: Shirosaka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.|Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: PRESTO, Japan Science and Technology Agency, Tokyo 102-8666, Japan.|Laboratory of Microbiology and Infectious Diseases, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nishino
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010269:Paraquat / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007211:Indoles; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010269:Paraquat; D015534:Trans-Activators; C531999:RamA protein, Salmonella typhimurium; C485381:SoxS protein, Salmonella enterica; C030374:indole