Role of Glutathione in Polyamine-Mediated beta-lactam Susceptibility in Pseudomonas aeruginosa.

摘要

Pseudomonas aeruginosa PAO1 is a Gram-negative opportunistic human pathogen that contributes to a wide variety of disorders, most important being cystic fibrosis. beta-lactam antibiotics have long been the novel drugs for the treatment of Pseudomonal infections, but the increasing emergence of antibiotic resistant strains has limited the therapeutic options available today. Combination therapy is a possible treatment option, involving the addition of natural nontoxic compounds to current antibiotics to increase their effectiveness. One compound that has shown potential in conjunction with beta-lactam antibiotics are polyamines. This study is aimed to better understand the mechanism that allows polyamines to improve the activity of antibiotics. A mutant Pseudomonas aeruginosa PAO1 strain was constructed that lacks a functional PA1807 hypothetical transporter gene. The antibiotic susceptibility of the PA1807 mutant was tested against wild type PAO1 to measure changes in antibiotic susceptibility in the presence of exogenous polyamines. Data shows that the mutant PA1807 showed a diminished susceptibility towards beta-lactam antibiotics in the presence of polyamines. The intracellular glutathione concentrations were also higher in the mutants showing that they are part of the glutathione transport system. This suggests that exogenous polyamines affect intracellular glutathione concentrations by forcing glutathione out of the cell. Without adequate concentrations of intracellular glutathione, Pseudomonas aeruginosa becomes more susceptible to the beta-lactam antibiotics.