Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci

Abstract

The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes from seven ciprofloxacin-resistant (Cp(r)) isolates of viridans group streptococci (two high-level Cp(r) Streptococcus oralis and five low-level Cp(r) Streptococcus mitis isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of the parE and gyrB genes from the five low-level Cp(r) S. mitis isolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cp(r) isolates had changes affecting the subunits of DNA topoisomerase IV: three in Set-79 (to Phe or Ile) of ParC and one in ParE at a position not previously described to be involved in quinolone resistance (Pro-424). One isolate did not show any mutation. The two high-level Cp(r) S. oralis isolates showed mutations affecting equivalent residue positions of Parc and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Tyr, respectively. The parC mutations were able to transform Streptococcus pneumoniae to ciprofloxacin resistance, while the gyrA mutations transformed S. pneumoniae only when mutations in parc were present. These results suggest that DNA topoisomerase IV is a primary target of ciprofloxacin in viridans group streptococci, DNA gyrase being a secondary target.