Quinolone-resistant gyrase mutants demonstrate decreased susceptibility to triclosan

Research output: Contribution to journalArticle

Authors

  • Liam S Redgrave
  • Gyles Ifill
  • Lesley A Mitchenall
  • Carly Webb
  • Robyn Iddles
  • Anthony Maxwell

External organisations

  • Institute of Microbiology & Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B152TT, UK.
  • The Quadram Institute, Norwich Research Park, Norwich NR47UH, UK.
  • Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR47UH, UK.

Abstract

Objectives: Cross-resistance between antibiotics and biocides is a potentially important driver of MDR. A relationship between susceptibility of Salmonella to quinolones and triclosan has been observed. This study aimed to: (i) investigate the mechanism underpinning this; (ii) determine whether the phenotype is conserved in Escherichia coli; and (iii) evaluate the potential for triclosan to select for quinolone resistance.

Methods: WT E. coli, Salmonella enterica serovar Typhimurium and gyrA mutants were used. These were characterized by determining antimicrobial susceptibility, DNA gyrase activity and sensitivity to inhibition. Expression of stress response pathways (SOS, RpoS, RpoN and RpoH) was measured, as was the fitness of mutants. The potential for triclosan to select for quinolone resistance was determined.

Results: All gyrase mutants showed increased triclosan MICs and altered supercoiling activity. There was no evidence for direct interaction between triclosan and gyrase. Identical substitutions in GyrA had different impacts on supercoiling in the two species. For both, there was a correlation between altered supercoiling and expression of stress responses. This was more marked in E. coli, where an Asp87Gly GyrA mutant demonstrated greatly increased fitness in the presence of triclosan. Exposure of parental strains to low concentrations of triclosan did not select for quinolone resistance.

Conclusions: Our data suggest gyrA mutants are less susceptible to triclosan due to up-regulation of stress responses. The impact of gyrA mutation differs between E. coli and Salmonella. The impacts of gyrA mutation beyond quinolone resistance have implications for the fitness and selection of gyrA mutants in the presence of non-quinolone antimicrobials.

Details

Original languageEnglish
Pages (from-to)2755-2763
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume72
Issue number10
Early online date3 Jul 2017
Publication statusPublished - 1 Oct 2017