Effect of Ciprofloxacin concentration on the frequency and nature of resistant mutants selected from Pseudomonas aeruginosa mutS and mutT hypermutators

MORERO NATALIA R.; MONTI MARIELA R.; ARGARAÑA CARLOS E.

AMER SOC MICROBIOLOGY

Año: 2011 vol. 55 p. 3668 - 3668

he rapid emergence of drug resistance upon treatment of Pseudomonas aeruginosa infections with fluoroquinolones is a serious concern. In this study, we report the effect of hypermutability on the mutant selection window for ciprofloxacin (CIP) by comparing the hypermutator MPAO1 mutS and mutT strains with the wild-type strain. The mutant selection window was shifted to higher CIP concentrations for both hypermutators, presenting the mutS strain with a broader selection window in comparison to the wild-type strain. The mutation prevention concentrations (MPC) determined for mutT and mutS strains were increased 2- and 4-fold over the wild-type level, respectively. In addition, we analyzed the molecular bases for resistance in the bacterial subpopulations selected at different points in the window. At the top of the window, the resistant clones isolated were mainly mutated in GyrA and ParC topoisomerase subunits, while at the bottom of the window, resistance was associated with the overe