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铜绿假单胞菌是一系列严重化脓性感染的重要致病菌，具有天然的和后天获得的耐药性，临床治疗很棘手。本论文了解了铜绿假单胞菌外膜微孔蛋白的性质，研究了铜绿假单胞菌外膜通透性与耐药性之间的关系，并在此基础上建立作用于外膜的抗铜绿假单胞菌药物的定向初筛方法。在研究铜绿假单胞菌外膜微孔蛋白性质时，选用了铜绿假单胞菌标准菌株ＰＡＯ１，以ＥＤＴＡ－溶菌酶法与超速离心法提取其外膜蛋白，ＳＤＳ－ＰＡＧＥ分析外膜蛋白图谱，并利用ＤＥＡＥ离子交换高效液相色谱柱加以纯化，通过重建蛋白脂质体测定了不同药物对外膜的通透作用。该部分实验结果证实了铜绿假单胞菌外膜微孔蛋白ＯｐｒＣ（分子量７０ｋＤ）、ＯｐｒＤ２（４６ｋＤ）和ＯｐｒＥ（４３ｋＤ）能够形成小孔道，具有通透功能。小分子亚胺培南（碳青霉烯类）能选择性通过ＯｐｒＤ２通道进入胞内
Pseudomonas aeruginosa is an important pathogen of a series of severe purulent infections, with natural and acquired resistance, clinical treatment is very difficult. In this paper, the properties of Pseudomonas aeruginosa outer membrane microporous protein were studied. The relationship between Pseudomonas aeruginosa outer membrane permeability and drug resistance was studied. Based on this, Directed screening of Pseudomonas aeruginosa drugs. In the study of Pseudomonas aeruginosa membrane microporous protein nature, the selection of the standard strain of Pseudomonas aeruginosa PAO1, EDTA-lysozyme method and ultracentrifugation method to extract the outer membrane protein, SDS-PAGE analysis of the outer membrane protein profile , And purified by DEAE ion exchange HPLC column. The permeation of different drugs on the outer membrane was determined by reconstituting the protein liposomes. This part of the experimental results confirmed that Pseudomonas aeruginosa outer membrane micropore protein OprC (molecular weight 70kD), OprD2 (46kD) and OprE (43kD) to form a small pore, with permeability. The small molecule imipenem (carbapenem) can selectively enter the intracellular via the OprD2 channel