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 regio ns (QRDRs) of the parC and gyrA genes from seven ciprofloxacin-resista nt (Cp-r) isolates of viridans group streptococci (two high-level Cp-r Streptococcus oralis and five low-level Cp-r Streptococcus mitis isol ates) were determined and compared with those obtained from susceptibl e 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 NCT C 12261 type strain were also analyzed. Four of these low-level Cp-r i solates had changes affecting the subunits of DNA topoisomerase IV: th ree in Ser-79 (to Phe or Ile) of ParC and one in ParE at a position no t previously described to be involved in quinolone resistance (Pro-424 ). One isolate did not show any mutation. The two high-level Cp-r S. o ralis isolates showed mutations affecting equivalent residue positions of ParC and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Yyr, res pectively. The parC mutations were able to transform Streptococcus pne umoniae to ciprofloxacin resistance, while the gyrA mutations transfor med S. pneumoniae only when mutations in parC were present. These resu lts suggest that DNA topoisomerase IV is a primary target of ciproflox acin in viridans group streptococci, DNA gyrase being a secondary targ et.