作用于铜绿假单胞菌外排泵的药物筛选模型的建立及初步应用

Study and primary application of the screening model for anti-Pseudomonas aeruginosa drugs with efflux pumps as a target

铜绿假单胞菌是耐药性十分突出的一类院内感染条件致病革兰氏阴性细菌 ,根据外排泵是铜绿假单胞菌产生耐药性的主要原因这一原理 ,以铜绿假单胞菌的外排泵为靶点 ,用过量表达外排泵的铜绿假单胞菌 Y5和外膜微孔蛋白 (Opr D2 )缺陷菌株 72 0 8以及铜绿假单胞菌标准菌株 PAO1建立了一个作用于铜绿假单胞菌外排泵的药物筛选模型。应用此模型可以初筛作用于铜绿假单胞菌外排泵的药物以及与现有已知的抗生素有协同作用的活性物质的筛选。应用所建立的方法从 2 44 9株微生物发酵液中 (真菌 170 0株 ,放线菌70 0株 ,海洋细菌 49株 )筛选得到 4株阳性菌 ,多次发酵表明这 4株阳性菌产生抗铜绿假单胞菌的活性物质的性质比较稳定 。

Pseudomonas aeruginosa is a very important clinical conditional pathogenic Gram Negative strain with high-level multi-drug resistance (MDR). Considering the fact that efflux pumps in Pseudomonas aeruginosa play a major role in this high-level MDR, we established a screening model for anti- Pseudomonas aeruginosa drugs using the Pseudomonas aeruginosa strains,i.e. one with over expresses efflux pumps (Y5 strain); the other losing the outer membrane protein -OprD2 (7208), and the standard strain-PAO1. We selected 4 positive strains out of 2449 microbes′ fermentation liquor which consist of 1700 fungus, 700 actinomycets and 49 strains of marine bacteria. The culture characteristic is fairly stable by several times of fermentation. Further studies of the positive material is on the way.