title: Evidence that a novel quaternary compound and its organic N-chloramine derivative do not select for resistant mutants of Pseudomonas aeruginosa.
abstract: BACKGROUND
  Pseudomonas aeruginosa is well known for causing hospital-acquired infections that are often difficult to treat because of its high intrinsic and acquired resistance to antibiotics. Resistance-nodulation-division (RND) efflux pumps are the major contributors to the intrinsic multidrug resistance (MDR) in this organism. Various biocides used in hospital settings have been shown to select for RND-pump-overexpressing mutants of P. aeruginosa that show cross-resistance to clinically relevant antibiotics. Therefore, finding biocides that do not select for multidrug-resistant mutants is important in controlling the spread of bacteria such as P. aeruginosa.
  
  
  OBJECTIVE
  To evaluate the potential of a novel quaternary ammonium compound and its N-chloramine derivative in selecting for MDR mutants of P. aeruginosa.
  
  
  METHODS
  P. aeruginosa PA01 was cultured in the presence of increasing concentrations of the quaternary ammonium compound and its N-chloramine derivative respectively, and one mutant each selected. Susceptibility of the mutants to both compounds as well as antibiotics was tested. Susceptibility of P. aeruginosa strains with deletions in RND pumps was also tested for both compounds to determine whether they are a substrate of these pumps. Expression of mexB, mexD, and mexY genes in the mutants was analysed using quantitative reverse transcriptase-polymerase chain reaction to determine whether the compounds can select for pump-overexpressing mutants.
  
  
  RESULTS
  We show that whereas both compounds can be pumped by the MexCD-OprJ pump, they neither select for mutants that overexpress RND pumps nor for mutants that display cross-resistance to antibiotics.
  
  
  CONCLUSIONS
  These compounds are promising candidates to be used as disinfectants in hospital settings.
authors.affiliation: Department of Microbiology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: M
authors.initials: M
authors.lastname: De Silva
authors.affiliation: Department of Textile Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Ning
authors.affiliation: Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ghanbar
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Zhanel
authors.affiliation: Department of Surgery, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Logsetty
authors.affiliation: Department of Textile Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Microbiology, University of Manitoba, Winnipeg, MB, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. Electronic address: Ayush.Kumar@umanitoba.ca.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D002700:Chloramines / Q000494:pharmacology*; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D002700:Chloramines; D000644:Quaternary Ammonium Compounds
keywords: Cross-resistance; N-Chloramine; Pseudomonas aeruginosa; Quaternary ammonium compounds; RND efflux pumps