Type II topoisomerase mutations in clinical isolates of Enterobacter cloacae and other enterobacterial species harbouring the qnrA gene.
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.
Lascols
Christine
C
Université Paris 12, CHU Henri Mondor, AP-HP, Bactériologie-Virologie-Hygiène, Créteil, France.
Robert
Jérôme
J
Cattoir
Vincent
V
Bébéar
Cécile
C
Cavallo
Jean-Didier
JD
Podglajen
Isabelle
I
Ploy
Marie-Cécile
MC
Bonnet
Richard
R
Soussy
Claude-James
CJ
Cambau
Emmanuelle
E
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
D015363:Quinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II