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dc.contributor.authorAdisak Romsangen_US
dc.contributor.authorPanithi Leesukonen_US
dc.contributor.authorJintana Duangnkernen_US
dc.contributor.authorPaiboon Vattanaviboonen_US
dc.contributor.authorSkorn Mongkolsuken_US
dc.contributor.otherChulabhorn Research Instituteen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherThailand Ministry of Educationen_US
dc.identifier.citationInternational Journal of Antimicrobial Agents. Vol.45, No.3 (2015), 314-318en_US
dc.description.abstract© 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. 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 ΔgrxD mutant strain was constructed. The ΔgrxD 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 ΔgrxD 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 ΔgrxD 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 2,2′-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.en_US
dc.rightsMahidol Universityen_US
dc.titleMutation of the gene encoding monothiol glutaredoxin (GrxD) in Pseudomonas aeruginosa increases its susceptibility to polymyxinsen_US
Appears in Collections:Scopus 2011-2015

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