title: Mutational upregulation of a resistance-nodulation-cell division-type multidrug efflux pump, SdeAB, upon exposure to a biocide, cetylpyridinium chloride, and antibiotic resistance in Serratia marcescens.
abstract: Serratia marcescens is an important opportunistic pathogen in hospitals, where quaternary ammonium compounds are often used for disinfection. The aim of this study is to elucidate the effect of a biocide on the emergence of biocide- and antibiotic-resistant mutants and to characterize the molecular mechanism of biocide resistance in Serratia marcescens. A quaternary ammonium compound-resistant strain, CRes01, was selected by exposing a wild-type strain of S. marcescens to cetylpyridinium chloride. The CRes01 cells exhibited 2- to 16-fold more resistance than the wild-type cells to biocides and antibiotics, including cetylpyridinium chloride, benzalkonium chloride, chlorhexidine gluconate, fluoroquinolones, tetracycline, and chloramphenicol, and showed increased susceptibilities to beta-lactam antibiotics and N-dodecylpyridinium iodide. Mutant cells accumulated lower levels of norfloxacin than the parent cells in an energized state but not in a de-energized state, suggesting that the strain produced a multidrug efflux pump(s). To verify this assumption, we knocked out a putative efflux pump gene, sdeAB, in CRes01 and found that the knockout restored susceptibility to most quaternary ammonium compounds and antibiotics, to which the CRes01 strain showed resistance. On the basis of these and other results, we concluded that S. marcescens gains resistance to both biocides and antibiotics by expressing the SdeAB efflux pump upon exposure to cetylpyridinium chloride.
authors.affiliation: Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan. maseda@bio.tokushima-u.ac.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Maseda
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hashida
authors.forename: Rumi
authors.initials: R
authors.lastname: Konaka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shirai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kourai
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002594:Cetylpyridinium / Q000494:pharmacology*; D004202:Disinfectants / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009643:Norfloxacin / Q000378:metabolism / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012706:Serratia marcescens / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004202:Disinfectants; D008565:Membrane Proteins; D000644:Quaternary Ammonium Compounds; D002594:Cetylpyridinium; D009643:Norfloxacin