title: Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates ofPseudomonas aeruginosaDiffers by Type III Secretion Genotype.
abstract: Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains ofPseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing theexoUgene of the type III secretion system are more likely to be FQ-resistant than strains containing theexoSgene, as well as more likely to acquire resistance-conferring mutations ingyrA/BandparC/E. We hypothesize that FQ-resistance imposes a lower fitness cost onexoUcompared toexoSstrains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation inparCfrom threeexoUto threeexoSclinical isolates and tested fitnessin vitrousing head-to-head competition assays. The mutation differentially affected fitness in theexoUandexoSstrains tested. While the addition of theparCmutation dramatically increased fitness in one of theexoUstrains leaving the other two unaffected, all threeexoSstrains displayed a general decrease in fitness. In addition, we found thatexoUstrains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to theexoSstrains. These results may provide a biological explanation for the observed predominance of the virulentexoUgenotype 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 ofP. aeruginosa. 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.
authors.affiliation: School of Pharmacy, University of Southern California Los Angeles, CA, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Agnello
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California Los Angeles, CA, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Finkel
authors.affiliation: School of Pharmacy, University of Southern California Los Angeles, CA, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Wong-Beringer
keywords: Pseudomonas aeruginosa; fitness; fluoroquinolone resistance; type III secretion; virulence