Faculty Mentor
Dong Kwon
Major/Area of Research
Biology
Description
Background: Pseudomonas aeruginosa is a major causative agent of hospital- and community-acquired infections. Antibacterial treatment of the infections is often difficult due to presence of antibiotic resistant P. aeruginosa. A number of intrinsic and acquired antibiotic resistance mechanisms reported in P. aeruginosa. Recently, scavenging intracellular reactive oxygen species (ROS) has suggested as an intrinsic antibiotic resistance mechanism to all bacterial species since antibiotics induce oxidative stress in the bacterial species. However, this intrinsic resistance mechanism is currently controversial and further clarification requires. Glutathione is a sulfuhydryl (-SH)-containing tri-peptide intracellular antioxidant and serves as a scavenger of the intracellular ROS. Aim: In this study, a mutant P. aeruginosa knocked-out a gene (gshA) encoding glutathione synthetase, a gshA-complemented mutant P. aeruginosa, and their parental wild type (MPAO1) used to understand the role of glutathione in the neutralization of oxidative stress (H2O2) and antibiotic susceptibility. Approaches and Results: Bacterial killing assays showed that the mutant strain (gshA::Tn-Tc) was completely killed at 0.005% of H2O2 while the gshA-complemented and their parental strains were both completely killed at 0.01% of H2O2. Antibiotic susceptibility testing showed that the mutant strain was at least 2-fold more susceptible to all tested antibiotics than that of its parental strain. The gshA-complemented strain fully restored the susceptibility to the same antibiotics as the same levels of the parental strain. Conclusions and Discussion: The results indicate that i) glutathione is associated with neutralization of oxidative stress, ii) antibiotics induce the oxidative stress, and iii) the antibiotic-induced oxidative stress in the mutant strain may have more ROS than its parental strain which results in the increased-susceptibility to antibiotics. Overall, the results suggest that glutathione is one of the intrinsic antibiotic resistance mechanisms and may be a possible drug target to treat the untreatable multidrug resistant P. aeruginosa.
Included in
A Role of Glutathione-Encoding Gene (gshA) in Oxidative Stress and Antibiotic Susceptibility in Multidrug Resistant Pseudomonas aeruginosa: A Possible Drug Target
Background: Pseudomonas aeruginosa is a major causative agent of hospital- and community-acquired infections. Antibacterial treatment of the infections is often difficult due to presence of antibiotic resistant P. aeruginosa. A number of intrinsic and acquired antibiotic resistance mechanisms reported in P. aeruginosa. Recently, scavenging intracellular reactive oxygen species (ROS) has suggested as an intrinsic antibiotic resistance mechanism to all bacterial species since antibiotics induce oxidative stress in the bacterial species. However, this intrinsic resistance mechanism is currently controversial and further clarification requires. Glutathione is a sulfuhydryl (-SH)-containing tri-peptide intracellular antioxidant and serves as a scavenger of the intracellular ROS. Aim: In this study, a mutant P. aeruginosa knocked-out a gene (gshA) encoding glutathione synthetase, a gshA-complemented mutant P. aeruginosa, and their parental wild type (MPAO1) used to understand the role of glutathione in the neutralization of oxidative stress (H2O2) and antibiotic susceptibility. Approaches and Results: Bacterial killing assays showed that the mutant strain (gshA::Tn-Tc) was completely killed at 0.005% of H2O2 while the gshA-complemented and their parental strains were both completely killed at 0.01% of H2O2. Antibiotic susceptibility testing showed that the mutant strain was at least 2-fold more susceptible to all tested antibiotics than that of its parental strain. The gshA-complemented strain fully restored the susceptibility to the same antibiotics as the same levels of the parental strain. Conclusions and Discussion: The results indicate that i) glutathione is associated with neutralization of oxidative stress, ii) antibiotics induce the oxidative stress, and iii) the antibiotic-induced oxidative stress in the mutant strain may have more ROS than its parental strain which results in the increased-susceptibility to antibiotics. Overall, the results suggest that glutathione is one of the intrinsic antibiotic resistance mechanisms and may be a possible drug target to treat the untreatable multidrug resistant P. aeruginosa.