title: Variation in the mutation frequency determining quinolone resistance in Chlamydia trachomatis serovars L2 and D.
abstract: OBJECTIVE
  Quinolone resistance of chlamydiae is supposed to be extremely rare. To assess the risk for the emergence of chlamydial quinolone resistance, we analysed the occurrence of resistant mutants in a quantitative perspective.
  
  
  METHODS
  Infectious elementary bodies of Chlamydia trachomatis serovar L(2) (ATCC VR-902B) and D (ATTC VR-885) clones were purified on density gradients, and mutants resistant to moxifloxacin and rifampicin were selected by a plaque assay. Plaque assays were conducted with 2 x 10(9) inclusion forming units (IFUs) of each serovar for rifampicin and 2.66 x 10(9) IFUs for moxifloxacin. Resistant clones were analysed for mutations in the gyrA, gyrB, parC and parE genes, and respective MICs were determined by titration experiments.
  
  
  RESULTS
  Mutation frequencies for rifampicin (MIC >or= 0.2 mg/L) did not differ significantly between serovars L(2) and D (5.7 x 10(-7) versus 6.3 x 10(-7)). In contrast, the occurrence of moxifloxacin-resistant mutants (MIC >or= 0.6 mg/L) was determined to be 2.0-2.2 x 10(-8) for the serovar L(2) isolate and less than 2.66 x 10(-9) for the serovar D isolate. Moxifloxacin resistance of all serovar L(2) clones depended on single-nucleotide point mutations in the quinolone resistance-determining region of the gyrA, whereas no additional mutations were found in the gyrB, parC or parE genes.
  
  
  CONCLUSIONS
  C. trachomatis isolates have the potential to present with clinically relevant antibiotic resistance in future. Serovar-specific differences in the occurrence of spontaneous mutations should be taken into account to predict quinolone resistance in different chlamydial diseases.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.forename: Jens
authors.initials: J
authors.lastname: Gieffers
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D024841:Fluoroquinolones; D005798:Genes, Bacterial; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009154:Mutation; D011804:Quinolines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D011804:Quinolines; D015363:Quinolones; D000077266:Moxifloxacin; D012293:Rifampin