Fluoroquinolone Resistance Mechanism of Clinical Isolates and Selected Mutants of Pasteurella multocida from Bovine Respiratory Disease in China

The minimum inhibitoryconcentrations (MICs), mutation prevention concentrations (MPCs) and contribution ofquinolone resistance-determining region (QRDR) mutations to fluoroquinolone(ciprofloxacin, enrofloxacin and orbifloxacin) susceptibility in 23 Pasteurellamultocida (Pm) isolates were investigated.Fluoroquinolone-susceptible isolates (MICs ≤0.25 µg/ml,9 isolates) had no QRDR mutations, and their respective MPCs were low.Fluoroquinolone-intermediate isolates (MICs=0.5 µg/ml,14 isolates) had QRDR mutations (Asp87 to Asn or Ala84 to Pro in gyrA),and their respective MPCs were high (4–32 µg/ml).First-step mutants (n=5) and laboratory-derived highly resistant fluoroquinolone mutants(n=5) also had QRDR mutations. The MICs of fluoroquinolones for mutant-derived strainswere decreased in the presence of efflux inhibitors. The results indicated that thefluoroquinolone resistance of Pm is mainly due to multiple target genemutations in gyrA and parC and the overexpression ofefflux pump genes.