Role of DNA repair mechanisms in the response of Pseudomonas aeruginosa to antimicrobials ciprofloxacin and ceftazidime

Abstract

The high incidence of multidrug-resistant Pseudomonas aeruginosa isolates is of extreme concern for the medical and scientific community. It is related to high mortality in patients with cystic fibrosis. Inappropriate antimicrobial therapy and the presence of sub-lethal concentrations of drugs in the environment has been associated with the induction of mutagenesis, bacterial resistance, and selection of mutants adapted to stress. Mutations may be caused by exogenous agents such as antimicrobials or as a result of metabolism when the organism is exposed to a stress. The antibiotics ciprofloxacin and ceftazidime, which directly or indirectly can cause DNA damage, can activate the SOS system, which expresses genes encoding the low-fidelity polymerases. In this case, DNA replication continues even in the presence of injury genome, in a process that can cause mutations. The imuAB dnaE2 operon is present in P. aeruginosa, and has been related to increased mutation rates and drug resistance in Caulobacter crescentus. The function of this operon has not been evaluated in P. aeruginosa. Therefore, it is important to study the nature of the mutagenesis mechanisms induced by antibiotics Ciprofloxacin and Ceftazidime, assessing the SOS response to beta-lactams and the function of error-prome DNA polymerases. Other DNA repair mechanisms will also be investigated. These studies involve the identification of targets for drug design that may increase the efficacy of treatment or reducing the risk of developing resistance.