title: Phenotype microarray analysis of the drug efflux systems in Salmonella enterica serovar Typhimurium.
abstract: A large number of drug efflux transporters have been identified in Salmonella enterica serovar Typhimurium, and increased expression of these transporters confers drug resistance in this organism. Here we compared the respiration activities of the wild-type strain and a mutant with nine deleted transporters by phenotype microarray analysis. The mutant was susceptible to 66 structurally unrelated compounds including many antibiotics, dyes, detergents, antihistamine agents, plant alkaloids, antidepressants, antipsychotic drugs, and antiprotozoal drugs. To investigate the effect of each transporter on the susceptibilities to these drugs, we used the single transporter mutants, several multiple deletion mutants, and the transporter overexpressor strains to determine minimum inhibitory concentrations of ampicillin, erythromycin, minocycline, ciprofloxacin, orphenadrine, amitriptyline, thioridazine, and chlorpromazine. The data indicate that the increased susceptibilities of the mutant lacking nine transporter genes are mainly dependent on the absence of the acrAB efflux genes as well as the tolC gene. In addition to the AcrAB-TolC efflux system, the results from the overexpressor strains show that AcrEF confers resistance to these compounds as well as AcrAB of Escherichia coli, MexAB-OprM and MexXY-OprM of Pseudomonas aeruginosa. The results highlight the importance of the efflux systems not only for resistance to antibiotics but also for resistance to antihistamine agents, plant alkaloids, antidepressants, antipsychotic drugs, and antiprotozoal drugs.
authors.affiliation: Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Hayashi-Nishino
authors.affiliation: Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: nishino@sanken.osaka-u.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nishino
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics*; D065288:Serogroup
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins
keywords: Bacteria; Multidrug efflux pump; Multidrug resistance; S. enterica