ARGARAÑA CARLOS ENRIQUE
Congresos y reuniones científicas
Título:
P. aeruginosa AND CIPROFLOXACIN, BACTERIAL RESISTANCE MECHANISM AND MUTAGENIC EFFECT OF THE DRUG
Autor/es:
MORERO NR
Lugar:
Puerto Madryn
Reunión:
Congreso; XLVI Reunión Anual de SAIB; 2010
Institución organizadora:
SAIB
Resumen:
Although Ciprofloxacin (CIP) is one of the most effective antibiotics against P. aeruginosa infections, resistance to this drug emerges quickly in the clinical setting, and is often linked to crossresistance to other antibiotics. Resistance of P. aeruginosa to CIP is mainly due to mutations in Gyr A and P arC subunits of the DNA topoisomerases, and the expression of multidrug efflux pump MexC D-OprJ by mutations in the transcriptional repressor N fxB. We analyzed the molecular nature of CIP resistance at different drug concentration for the PAO1 wild type and hypermutator strains defective in the Mismatch and 8-oxoguanine Repair Systems (MRS and GO respectively). We report the main resistance pathway and mutational spectrum for each strain, and
show that gyrA is mainly mutated in cells selected at high CIP concentrations, while nfxB mutations are dominant at low drug doses. It was also observed that: a) nfxB mutants showed crossresistance to other antibiotics; b) double mutant gyrA/parC cells were generated in hypermutator MRS defective strain at a higher proportion than expected; c) oxidative stress stimulate the mutation frequency in GO defective strains; and d) nfxB mutants emerge at a
very high frequency when cells are grown at subinhibitory levels of CIP. Different experimental approaches indicated that this last phenomenon is due to a direct effect of CIP on the bacterial cells.
show that gyrA is mainly mutated in cells selected at high CIP concentrations, while nfxB mutations are dominant at low drug doses. It was also observed that: a) nfxB mutants showed crossresistance to other antibiotics; b) double mutant gyrA/parC cells were generated in hypermutator MRS defective strain at a higher proportion than expected; c) oxidative stress stimulate the mutation frequency in GO defective strains; and d) nfxB mutants emerge at a
very high frequency when cells are grown at subinhibitory levels of CIP. Different experimental approaches indicated that this last phenomenon is due to a direct effect of CIP on the bacterial cells.
