Pseudomonas aeruginosa （P. aeruginosa） is one of the leading pathogens involved in nosocomial pneumonia. In addition, P. aeruginosa infection is associated with significant morbidity and mortality. A major problem i...Pseudomonas aeruginosa （P. aeruginosa） is one of the leading pathogens involved in nosocomial pneumonia. In addition, P. aeruginosa infection is associated with significant morbidity and mortality. A major problem in P. aeruginosa infection is that this organism exhibits natural and acquired resistance to many structurally and functionally diverse antibiotics.展开更多
Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which...Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which contribute greatly to the multidrug resistance of P. aeruginosa. Effiux pump inhibitors （EPIs） of MexAB-OprM could enhance the activity of the antibiotics effiuxed by MexAB-OprM, and thus they might be useful in the clinic as antibacterial synergistic agents. In this work, a new EPI of MexAB-OprM, KL-0153, was discovered by screening of a small molecular library. Its inhibition of MexAB-OprM was confirmed by assays of synergistic activity and EB accumulation. The activity of KL-0153 was shown to be synergistic with antibiotics effiuxed by MexAB-OprM when they were tested against strains expressing MexAB-OprM, especially so for the strains that express MexAB-OprM at high levels. KL-0153 showed more activity than the positive drug carbonyl cyanide m-chlorophenylhydrazone in the EB accumulation assay. It cannot be neglected that KL-0153 has significant liver and kidney toxicity. However, KL-0153 may be a lead comoound for the research and development of new tvoes of EPIs.展开更多
文摘Pseudomonas aeruginosa （P. aeruginosa） is one of the leading pathogens involved in nosocomial pneumonia. In addition, P. aeruginosa infection is associated with significant morbidity and mortality. A major problem in P. aeruginosa infection is that this organism exhibits natural and acquired resistance to many structurally and functionally diverse antibiotics.
文摘Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which contribute greatly to the multidrug resistance of P. aeruginosa. Effiux pump inhibitors （EPIs） of MexAB-OprM could enhance the activity of the antibiotics effiuxed by MexAB-OprM, and thus they might be useful in the clinic as antibacterial synergistic agents. In this work, a new EPI of MexAB-OprM, KL-0153, was discovered by screening of a small molecular library. Its inhibition of MexAB-OprM was confirmed by assays of synergistic activity and EB accumulation. The activity of KL-0153 was shown to be synergistic with antibiotics effiuxed by MexAB-OprM when they were tested against strains expressing MexAB-OprM, especially so for the strains that express MexAB-OprM at high levels. KL-0153 showed more activity than the positive drug carbonyl cyanide m-chlorophenylhydrazone in the EB accumulation assay. It cannot be neglected that KL-0153 has significant liver and kidney toxicity. However, KL-0153 may be a lead comoound for the research and development of new tvoes of EPIs.
