Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Differs by Type III Secretion Genotype.

Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains of , limiting treatment options. We have reported previously that highly virulent strains containing the gene of the type III secretion system are more likely to be FQ-resistant than strains containing the gene, as well as more likely to acquire resistance-conferring mutations in and . We hypothesize that FQ-resistance imposes a lower fitness cost on compared to strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in from three to three clinical isolates and tested fitness using head-to-head competition assays. The mutation differentially affected fitness in the and strains tested. While the addition of the mutation dramatically increased fitness in one of the strains leaving the other two unaffected, all three strains displayed a general decrease in fitness. In addition, we found that strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the strains. These results may provide a biological explanation for the observed predominance of the virulent genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of . Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance.