Glutathione Reductase Encoding Gene (gor) is Associated with Oxidative Stress and Antibiotic Susceptibility in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is a major causative agent of the hospital- and community-acquired infections. These infections are often antibiotic resistant and difficult to treat. Several intrinsic and acquired resistance mechanisms to antibiotics have reported in P. aeruginosa. Recently, oxidative- stress-scavenging-systems have suggested as a possible intrinsic resistance mechanism to antibiotics because oxidative stresses induced by bactericidal antibiotics contribute to bacterial killing effects. However, this remains controversial such that further clarification is required. Glutathione reductase is a key enzyme in the maintenance of the optimum level of intracellular glutathione-redox potential to ensure normal functioning of cellular processes including the detoxification of oxidative stress. In this study, the role of a glutathione-reductase-encoding gene (gor) in oxidative stress and antibiotic susceptibility was determined in P. aeruginosa. Results showed that a gor-mutant strain was more susceptible to hydrogen peroxide (but not superoxide) than the parental strain and 100% of cells were killed with 0.01% hydrogen peroxide while the parental strain survived at the same concentration of hydrogen peroxide. The gor-mutant strain was also more susceptible to carbenicillin, chloramphenicol, ciprofloxacin, and tetracycline than the parental strain, which was confirmed by bacterial killing-kinetics. These results suggest that the gor gene is associated with oxidative stress and susceptibility to bactericidal as well as bacteriostatic antibiotics and that the oxidative-stress-scavenging-systems may be a possible drug-target for multidrug resistant P. aeruginosa.