title: Fluoroquinolone resistance mechanisms in multidrug-resistant Escherichia coli isolated from extraintestinal infections in dogs.
abstract: Fluoroquinolone resistance is an emerging problem in companion animal practice. The present study aimed to determine comparative fluoroquinolone minimum inhibitory concentrations (MICs) for enrofloxacin, marbofloxacin and pradofloxacin and identify plasmid-mediated quinolone resistance (PMQR) mechanisms in 41 multidrug-resistant (MDR) Escherichia coli isolates representing three main clonal groups (CGs) cultured from extraintestinal infections in dogs. All isolates were resistant to fluoroquinolones and the PMQR genes qnrA1, qnrB2, qnrS1 and qepA were identified in isolates from each CG. For a subset of 13 representative isolates, fluoroquinolone chromosomal resistance mechanisms were characterized. CG1 isolates had three mutations in the quinolone resistance determining region (QRDR), two in gyrA (Ser TCG-83→Leu TTG and Asp GAC-87→Asn AAC) and one in parC (Ser AGC-80→Ile ATT), whilst CG2 and CG3 isolates also possessed an additional mutation in parC (Glu GAA-84→Gly GGA) which was reflected in higher fluoroquinolone MICs compared to CG1. Organic solvent tolerance was demonstrated in 8 of the 13 isolates, and all 13 isolates demonstrated enhanced efflux on the basis of a 4-fold decrease or greater in the MIC of enrofloxacin when incubated with an efflux pump inhibitor. A mutation in acrR which can cause overexpression of the AcrAB multidrug efflux pump was detected in CG1 strains. These findings indicate that fluoroquinolone resistance in MDR E. coli isolated from extraintestinal infections in dogs is associated with a combination of target mutations in the QRDRs, transferable PMQR mechanisms and enhanced efflux.
authors.affiliation: The University of Queensland, School of Veterinary Science, Brisbane, QLD 4072, Australia. gibson.j@uq.edu.au
authors.forename: Justine S
authors.initials: JS
authors.lastname: Gibson
authors.forename: Rowland N
authors.initials: RN
authors.lastname: Cobbold
authors.forename: Myat T
authors.initials: MT
authors.lastname: Kyaw-Tanner
authors.forename: Peter
authors.initials: P
authors.lastname: Heisig
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Trott
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004269:DNA, Bacterial / Q000235:genetics; D004283:Dog Diseases / Q000188:drug therapy / Q000382:microbiology*; D004285:Dogs; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D024841:Fluoroquinolones / Q000494:pharmacology / Q000627:therapeutic use*; D005798:Genes, Bacterial / Q000235:genetics; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000662:veterinary; D017422:Sequence Analysis, DNA / Q000662:veterinary
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones