4.7 Article

TolC dependency of multidrug efflux systems in Salmonella enterica serovar Typhimurium

Journal

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 65, Issue 7, Pages 1372-1376

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/jac/dkq160

Keywords

drug efflux pumps; multidrug resistance; resistance-nodulation-division family

Funding

  1. Astellas Foundation for Research on Metabolic Disorders
  2. Research Foundation for Pharmaceutical Sciences
  3. Takeda Science Foundation
  4. Naito Foundation
  5. National Institute of Biomedical Innovation
  6. Ministry of Education, Culture, Sports, Science, and Technology of Japan
  7. Japan Society for the Promotion of Science
  8. PRESTO, Japan Science and Technology Agency, Japan

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Objectives: TolC is a major outer membrane channel and it plays an important role in the excretion of a wide range of molecules, including antibiotics. A recent study has shown that Salmonella enterica serovar Typhimurium has nine functional drug efflux pumps; however, the TolC dependency of these efflux pumps remains to be studied in detail. The aim of this study was to investigate the TolC dependency of multidrug efflux pumps in this organism. Methods: All genes encoding the drug efflux systems were cloned into the pUC118 vector. Constructed plasmids were transformed into Delta acrB and Delta tolC mutants of S. enterica serovar Typhimurium ATCC 14028s, and then the drug susceptibilities of these transformants were determined. Results: Plasmids carrying the acrAB, acrD, acrEF, mdsAB, mdtABC, emrAB or macAB genes did not confer resistance to the tolC mutant, whereas they conferred drug resistance to the acrB mutant. Only three plasmids carrying mdsABC, mdfA or mdtK conferred resistance to the tolC mutant. Conclusions: TolC is required for the function of seven drug efflux systems (AcrAB, AcrD, AcrEF, MdsAB, MdtABC, EmrAB and MacAB) in S. enterica serovar Typhimurium.

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