绿脓杆菌III型分泌系统的新抑制剂研究

项目名称： 绿脓杆菌III型分泌系统的新抑制剂研究

项目编号： No.21272029

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 陈新

作者单位： 常州大学

项目金额： 80万元

中文摘要： 大多数抗生素通常是抑制细菌的重要细胞生理功能，最后杀死细菌。但这种方法成为了导致细菌产生耐药性的主要选择压力，以致于出现了具有强耐药性的"超级细菌"。绿脓杆菌是一种革兰氏阴性机会性人类病原菌，它易感染免疫受损的人群。它对现有抗生素的敏感性很差，具有天然的耐药性，且很容易获得后天耐药性。III型分泌系统(T3SS)是绿脓杆菌引起和传播急性感染的致病因子，它能够将效应分子蛋白转运到宿主细胞中并导致其感染发病。本项目研究的T3SS抑制剂是以绿脓杆菌的T3SS为靶点，目标是抑制其传递毒力蛋白的功能与作用，阻止绿脓杆菌对宿主细胞的传染性，但并不是直接抑制该细菌的重要细胞生理功能。这是一种创新性和充满希望的策略，因为这样会大大降低绿脓杆菌发展耐药性突变的选择压力，从而有希望开发出一类与现有抗生素机制完全不同的新型抗菌剂。

中文关键词： 绿脓杆菌；III 型分泌系统；抑制剂；构效关系；火疫病

英文摘要： Most antibiotics affect cellular processes of microorganisms and therefore kill them, which becomes a strong selective pressure on them to develop resistance against antibiotics, and result in appearance of multiple antibiotic-resistant pathogens so called "super bacterium". Pseudomonas aeruginosa is an opportunistic human pathogenic Gram-negative bacterium which infects immunocompromised individuals. One of its most worrisome characteristics consists in its low antibiotic susceptibility. In addition to the natural resistance, this bacterium easily acquires posteriori drug resistances. P.aeruginosa carries type III secretion system (T3SS) as a major virulence determinant; via the T3SS, the bacterium secretes and injects effector proteins into target host cells, and trigger disease symptoms. This proposal seeks to develop potent small molecule inhibitors targeting the T3SS of P. aeruginosa, so as to prevent the bacterium from injecting effector proteins and causing pathophysiology to its host cells. Targeting the virulence of P.aeruginosa, rather than its survival, is an innovative and promising approach, which might be able to greatly reduce selection pressures on the pathogen to develop drug-resistant mutations. As a result, novel antimicrobials with completely different antibiotics mechanism from conventional

英文关键词： Pseudomonas aeruginosa；type III secretion system；inhibitors；structure-activity relationship；fire blight