Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6117814 | International Journal of Antimicrobial Agents | 2015 | 5 Pages |
Abstract
Pseudomonas aeruginosa is a frequent cause of hospital-acquired infections that have a high mortality rate because of its innate drug resistance. Polymyxins are recognised as the last-line antibiotics for the treatment of multidrug-resistant (MDR) P. aeruginosa. In this study, the link between monothiol glutaredoxin (GrxD), which catalyses the reduction of disulphide bonds of various substrates in P. aeruginosa, and antibiotic resistance was examined. A P. aeruginosa ÎgrxD mutant strain was constructed. The ÎgrxD mutant showed significantly increased susceptibility to polymyxin B (PMB) compared with the wild-type P. aeruginosa PAO1. Site-directed mutagenesis was performed to generate amino acid substitutions in GrxD, and the ability of mutated grxD genes to confer resistance to PMB in the ÎgrxD mutant was tested. The results indicated that residue C29 at the active site of GrxD is important for protection against polymyxin killing in the mutant. Polymyxin killing of PAO1 and the ÎgrxD mutant did not appear to involve hydroxyl radicals generated by antibiotic treatment because increased susceptibility of the mutant to PMB was also observed under anaerobic growth as well as aerobically in the presence of the iron chelator 2,2â²-dipyridyl. Thus, GrxD could be a target for the development of agents that enhance the effectiveness of PMB in treating clinically important MDR P. aeruginosa infections.
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Authors
Adisak Romsang, Panithi Leesukon, Jintana Duangnkern, Paiboon Vattanaviboon, Skorn Mongkolsuk,