Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa.

The target enzymes GyrA and ParC and two efflux pump regulatory genes mexR and nfxB were analysed to determine changes associated with fluoroquinolone resistance in Pseudomonas aeruginosa. Both low- and high-level ciprofloxacin resistance was associated with a Thr-83Ile substitution in GyrA. A ParC Ser-80Leu substitution was found in highly resistant isolates in tandem with the Thr-83Ile substitution in GyrA. Mutations in the efflux regulatory genes were associated with resistance only when in tandem with a mutation in GyrA or ParC. These data show that the main mechanism of fluoroquinolone resistance in P. aeruginosa is mediated primarily through mutations in GyrA, and that mutations in ParC and the efflux regulatory genes are secondary.