Fluoroquinolone Resistance Mutations in the parC , parE , and gyrA Genes of Clinical Isolates of Viridans Group Streptococci

The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of theparC andgyrA genes from seven ciprofloxacin-resistant (Cpr ) isolates of viridans group streptococci (two high-level Cpr Streptococcus oralis and five low-level Cpr Streptococcus mitis isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of theparE andgyrB genes from the five low-level Cpr S. mitis isolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cpr isolates had changes affecting the subunits of DNA topoisomerase IV: three in Ser-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 Cpr 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. TheparC mutations were able to transformStreptococcus pneumoniae to ciprofloxacin resistance, while thegyrA mutations transformedS. pneumoniae only when mutations inparC 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.