PARC SUBUNIT OF DNA TOPOISOMERASE-IV OF STREPTOCOCCUS-PNEUMONIAE IS APRIMARY TARGET OF FLUOROQUINOLONES AND COOPERATES WITH DNA GYRASE-A SUBUNIT IN FORMING RESISTANCE PHENOTYPE

The genes encoding the ParC and ParE subunits of topoisomerase IV of S treptococcus pneumoniae, together with the region encoding amino acids 46 to 172 (residue numbers are as in Escherichia coli) of the pneumoc occal GyrA subunit, were partially characterized, The gyrA gene maps t o a physical location distant from the gvrB and parC loci on the chrom osome, whereas parC is closely linked to parE. Ciprofloxacin-resistant (Cp(r)) clinical isolates of S. pneumoniae had mutations affecting am ino acid residues of the quinolone resistance-determining region of Pa rC (low-level Cp(r)) or in both quinolone resistance-determining regio ns of ParC and GyrA (high-level Cp(r)), Mutations were found in residu e positions equivalent to the serine at position 83 and the aspartic a cid at position 87 of the E. coli GyrA subunit. Transformation experim ents suggest that ParC is the primary target of ciprofloxacin. Mutatio n in parC appears to be a prerequisite before mutations in gyrA can in fluence resistance levels.