Evidence that a novel quaternary compound and its organic N-chloramine derivative do not select for resistant mutants of Pseudomonas aeruginosa

M De Silva; C Ning; S Ghanbar; G Zhanel; S Logsetty; S Liu; A Kumar

doi:10.1016/j.jhin.2015.05.009

Evidence that a novel quaternary compound and its organic N-chloramine derivative do not select for resistant mutants of Pseudomonas aeruginosa

J Hosp Infect. 2015 Sep;91(1):53-8. doi: 10.1016/j.jhin.2015.05.009. Epub 2015 Jun 16.

Authors

M De Silva¹, C Ning², S Ghanbar³, G Zhanel⁴, S Logsetty⁵, S Liu⁶, A Kumar⁷

Affiliations

¹ Department of Microbiology, University of Manitoba, Winnipeg, MB, Canada.
² Department of Textile Sciences, University of Manitoba, Winnipeg, MB, Canada.
³ Department of Chemistry, University of Manitoba, Winnipeg, MB, Canada.
⁴ Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
⁵ Department of Surgery, University of Manitoba, Winnipeg, MB, Canada.
⁶ 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.
⁷ 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.

PMID: 26122622
DOI: 10.1016/j.jhin.2015.05.009

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.

Aim: 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.

Findings: 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.

Conclusion: These compounds are promising candidates to be used as disinfectants in hospital settings.

Keywords: Cross-resistance; N-Chloramine; Pseudomonas aeruginosa; Quaternary ammonium compounds; RND efflux pumps.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Bacterial Outer Membrane Proteins / genetics
Bacterial Outer Membrane Proteins / metabolism
Chloramines / pharmacology*
Cross Infection / drug therapy
Cross Infection / microbiology
Cross Infection / prevention & control
Drug Resistance, Multiple, Bacterial
Humans
Microbial Sensitivity Tests
Mutation
Pseudomonas aeruginosa / drug effects*
Pseudomonas aeruginosa / genetics
Pseudomonas aeruginosa / isolation & purification
Pseudomonas aeruginosa / metabolism
Quaternary Ammonium Compounds / pharmacology*

Substances

Anti-Bacterial Agents
Bacterial Outer Membrane Proteins
Chloramines
Quaternary Ammonium Compounds