Evaluation of Prevalence of Classical Fluoroquinolone Resistance Mechanisms in Chlamydia trachomatis Due to Mutations in the Topoisomerase Genes

Abstract

Until now, mutational resistance to fluoroquinolones (FQs) that represent a second-line treatment option for chlamydial infections after macrolides and tetrxacyclines has not been described in clinical isolates of C. trachomatis. However, a possibility of selection of FQ resistance via mutations in the primary target gene, gyrA, has been demonstrated in vitro with C. trachomatis strains. In Russia, FQs are used widely and available over-the-counter thus potentially exerting significant selective pressure for resistance development in STI pathogens. This study aimed to assess the presence of any FQ resistance mutations in quinolone resistance determining regions (QRDRs) of the C. trachomatis gyrA and parC genes directly in clinical samples using a newly developed realtime PCR assay. A total of 1572 C. trachomatis-positive clinical samples, obtained from patients with various urogenital tract infections, and 200 negative samples (used for control of assay specificity) were screened. A single sample revealed the presence of an A/G nucleotide transition in the PCR probe binding site corresponding to the Ser-83/Gly amino acid substitution of in the GyrA QRDR which was confirmed by re-amplification and direct DNA sequencing. We, therefore, report for the first time the identification of a typical FQ resistance mutation in the C. trachomatis gyrA gene from a clinical sample. Results of our study, however, demonstrate that the «classical» resistance mechanisms to FQ are rare in the studied population of C. trachomatis.