Phenotype microarray analysis of the drug efflux systems in Salmonella enterica serovar Typhimurium

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2016-11, Vol.22 (11), p.780-784
• Main Authors: Yamasaki, Seiji, Fujioka, Takuma, Hayashi, Katsuhiko, Yamasaki, Suguru, Hayashi-Nishino, Mitsuko, Nishino, Kunihiko, Dr
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Bacteria; Bacterial Proteins - genetics; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; Escherichia coli - drug effects; Escherichia coli - genetics; Hematology, Oncology and Palliative Medicine; Membrane Transport Proteins - genetics; Microarray Analysis - methods; Microbial Sensitivity Tests - methods; Multidrug efflux pump; Multidrug resistance; Mutation - genetics; Phenotype; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; S. enterica; Salmonella typhimurium - drug effects; Salmonella typhimurium - genetics; Serogroup
• ISSN: 1341-321X; 1437-7780
• DOI: 10.1016/j.jiac.2016.03.015

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 is 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.