Objectives: 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 L2 (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 × 109 inclusion forming units (IFUs) of each serovar for rifampicin and 2.66 × 109 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 ≥ 0.2mg/L) did not differ significantly between serovars L2 and D (5.7 × 10-7 versus 6.3 × 10-7). In contrast, the occurrence of moxifloxacin-resistant mutants (MIC ≥ 0.6 mg/L) was determined to be 2.0-2.2 × 10-8 for the serovar L2 isolate and less than 2.66 × 10-9 for the serovar D isolate. Moxifloxacin resistance of all serovar L2 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.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)