医院感染在感染性疾病中占有相当比例。院内感染的病原菌中,铜绿假单胞菌的感染高居榜首,且耐药状况十分严重。主动外排系统是细菌存在耐药性并发生获得性多重耐药的主要原因。M exAB-OprM型外排系统因具有广谱的外排活性成为铜绿假单...医院感染在感染性疾病中占有相当比例。院内感染的病原菌中,铜绿假单胞菌的感染高居榜首,且耐药状况十分严重。主动外排系统是细菌存在耐药性并发生获得性多重耐药的主要原因。M exAB-OprM型外排系统因具有广谱的外排活性成为铜绿假单胞菌最具临床意义的药物外排系统。本文对细菌主动外排系统的分类,PA M exAB-OprM外排系统的组成、结构、重要作用及表达调控予以综述,并对其治疗研究作出展望。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
文摘医院感染在感染性疾病中占有相当比例。院内感染的病原菌中,铜绿假单胞菌的感染高居榜首,且耐药状况十分严重。主动外排系统是细菌存在耐药性并发生获得性多重耐药的主要原因。M exAB-OprM型外排系统因具有广谱的外排活性成为铜绿假单胞菌最具临床意义的药物外排系统。本文对细菌主动外排系统的分类,PA M exAB-OprM外排系统的组成、结构、重要作用及表达调控予以综述,并对其治疗研究作出展望。
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.
