INHIBITORY EFFECTS OF CIPROFLOXACIN AND SPARFLOXACIN ON DNA GYRASE PURIFIED FROM FLUOROQUINOLONE-RESISTANT STRAINS OF METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS

The activities of new quinolones against 140 strains of methicillin-resistant Staphylococcus aureus were determined. From the relationship between the MICs of sparfloxacin and ciprofloxacin, fluoroquinolone-resistant S. aureus 6171 (MIC of sparfloxacin, 200-mu-g/ml; MIC of ciprofloxacin, 100-mu-g/ml) and fluoroquinolone-susceptible S. aureus FDA 209-P were selected for purification of the subunit A and B proteins of their DNA gyrases. The supercoiling activities of reconstituted A(r)B(r) (r, resistant) (from strain 6171) and A(r)B(s) (s, susceptible) gyrases were 40-fold more resistant to new quinolones than those of A(s)B(s) from FDA 209-P and A(s)B(r) gyrases. The 50% inhibitory doses of ciprofloxacin and sparfloxacin for A(m)B(m) (from mutant 19) and A(m)B(s) (m, moderately resistant) gyrases were 15- to 27-fold higher than those for A(s)B(s) and A(s)B(m) gyrases. These findings indicate that one of the resistance mechanisms of S. aureus against fluoroquinolones is a modification of the gyrase subunit A protein.