Pseudomonas aeruginosa deficient in 8-oxodeoxyguanine repair system shows high frequency of resistance to ciprofloxacin

MORERO, N AND ARGARAÑA CE

FEMS MICROBIOLOGY LETTERS

Año: 2009 vol. 290 p. 217 - 226

0378-1097

The 8-oxodeoxyguanine repair system participates in the prevention and correction of mutations generated by oxidative DNA damage in prokaryotes and eukaryotes. In this study, we report that Pseudomonas aeruginosa strains deficient in this repair mechanism by inactivation of the mutT, mutM and mutY genes, generate a high frequency of cells resistant to the antibiotic ciprofloxacin. In the mutT strain the increase in ciprofloxacin resistance achieved at 3-fold MIC was about 1600-fold over the wild type level, similar to the frequency achieved by the mismatch repair deficient mutS strain. Molecular analysis of wild type, mutT and mutY clones resistant to ciprofloxacin indicated that the nfxB gene was mutated in the majority of the cases, while mutS-derived resistant clones were mainly mutated in gyrA and parC genes. Cell viability analysis after treatment with paraquat or hydrogen peroxide indicated that 8-oxodeoxyguanine repair-deficient strains were considerably more susceptible to oxidative stress than the parental strain. Finally, it is shown that ciprofloxacin resistance frequency of wild type and repair deficient strains increased significantly after cell exposure to paraquat. Thus, oxidative stress is strongly implicated in the emergence of ciprofloxacin resistant mutants in P. aeruginosa, and the 8-oxoG-repair pathway plays an important role in the prevention of these mutations.