title: Type II topoisomerase mutations in clinical isolates of Enterobacter cloacae and other enterobacterial species harbouring the qnrA gene.
abstract: The qnr genes are transferable genes that confer low-level quinolone resistance by protection of topoisomerase. The occurrence of mutations in DNA gyrase (gyrA, gyrB) and topoisomerase IV (parC, parE) genes in strains harbouring qnr was investigated in 28 qnrA-positive clinical isolates, among which 7 strains also harboured qnrS. Topoisomerase mutations were found in 25 (89%) of the 28 strains, with at least two mutations (gyrA and parC) in 13 strains and one mutation in 12 strains. Isolates of the Enterobacter cloacae complex were compared with reference strains of the new Enterobacter species. gyrA mutations were found at position 83 (Ser or Thr for Ile, Tyr, Leu or Phe depending on the species), and new gyrB mutations were described (S463A, S464F). qnrA had an additive effect of a 10-fold increase in the minimum inhibitory concentration (MIC) whatever the number of topoisomerase mutations, and qnrS was additive to qnrA with a further 2- to 10-fold increase in the MIC. Comparison of MICs with susceptibility breakpoints showed that strains combining qnrA and topoisomerase mutations were resistant to fluoroquinolones, but the three strains lacking a topoisomerase mutation were susceptible using ciprofloxacin and levofloxacin but not using nalidixic acid or moxifloxacin testing.
authors.affiliation: Université Paris 12, CHU Henri Mondor, AP-HP, Bactériologie-Virologie-Hygiène, Créteil, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lascols
authors.forename: Jérôme
authors.initials: J
authors.lastname: Robert
authors.forename: Vincent
authors.initials: V
authors.lastname: Cattoir
authors.forename: Cécile
authors.initials: C
authors.lastname: Bébéar
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Cavallo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Podglajen
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Ploy
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
authors.forename: Claude-James
authors.initials: CJ
authors.lastname: Soussy
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cambau
mesh_terms: D027081:DNA Gyrase / Q000187:drug effects / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000187:drug effects / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004754:Enterobacter / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D016972:Enterobacter cloacae / Q000187:drug effects / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010802:Phylogeny; D015363:Quinolones / Q000494:pharmacology; D017422:Sequence Analysis, DNA
chemical_list: D015363:Quinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II