Arcobacter butzleri Ciprofloxacin Resistance: Point Mutations in DNA Gyrase A and Role on Fitness Cost.

Arcobacter butzleri is a widely distributed emerging pathogen resistant to various classes of antimicrobial agents, namely fluoroquinolones. A. butzleri resistance to fluoroquinolones is conferred by point mutations at the antibiotic target. The aim of this study was to evaluate mutations at gyrA associated with ciprofloxacin resistance and evaluate whether acquisition of resistance impacts on fitness and stress tolerance of A. butzleri. A. butzleri ciprofloxacin mutants were generated by laboratory induction. Identification of mutations associated with ciprofloxacin resistance was performed by gyrA sequencing. Growth kinetics, cost of fitness, biofilm formation ability, and stress tolerance were assessed. Two amino acid substitutions in the quinolone resistance-determining region of GyrA were identified in the mutant strains, one previously described (Thr-85-Ile) and a new substitution (Asp-89-Tyr). No differences in growth kinetics were recorded between parental and mutant strains; however, fitness cost was variable, according to the genetic background of the strains, and independently of ciprofloxacin resistance. Overall, the ciprofloxacin resistance development did not significantly affect stress tolerance, motility, or biofilm-forming ability. In conclusion, acquisition of ciprofloxacin resistance in A. butzleri is associated with mutations in gyrA and is likely well compensated, with cost of fitness reflecting the diversity in genetic background of this bacterium.