幽门螺杆菌IV型分泌系统伴侣蛋白的功能与机制研究

幽门螺杆菌（HP）是胃部疾病的主要病原体，其感染在世界范围内流行，我国人群感染率近年呈上升趋势，达60%以上。研究表明：HP的毒力因子是通过Cag致病岛编码的IV型分泌系统转运进入宿主细胞而发挥致病作用。HP的IV型分泌系统是一个由14种结构蛋白和多种伴侣蛋白组成的复合体管道结构，跨越细菌内外膜，具有转运毒力因子、传递信号、诱导IL-8分泌等功能。目前结构蛋白的功能基本明确，伴侣蛋白的功能尚未十分清楚。本研究以伴侣蛋白（CagU、CagM、CagG及CagI）为研究对象，通过分子生物学、免疫学、微生物学及生物细胞学等技术探讨四种蛋白的亚细胞定位和状态；功能；相互间作用关系；对毒力因子分泌、生物膜形成的影响；在体内对HP致病性的影响等，旨在阐明四种伴侣蛋白在IV型分泌系统识别和转运毒力因子过程中的作用和机制；在体外对生物膜形成、在体内对致病性的影响。同时，为治疗HP感染提供新的药物作用靶点。

Helicobacter pylori（H.pylori）, one of the common pathogens associated with gastric diseases,is prevalent over the world.Recently the infection rate in our country has been rising up to over 60%.Previous studies have indicated that virulence factors of H.pylori are delivered into host cells via the type IV secretion system that encoded by the Cag pathogenicity island. The type IV secretion system is a multiple tunnel-like structure that is consist of 14 structural proteins and various chaperonins. The Cag T4SS, located on the bacteria membrane (including inner and outer membrane),has the major function of translocation of virulence factors, signal transduction and induction of IL-8.Although the characterization of the structural proteins have been identified,the characterization of the chaperonins remains unclear.This study is aimed at the T4SS chaperonins (CagU,CagM,CagG,CagI) and focused on their subcellular localization, function, interaction, mechanism in the process of reconizing and delivering virulence factors and involvement in the H.Pylori pathogenicity and biofilm formation .We explore the function of these genes through molecular biology, immunology and microbiology techniques.We intend to demonstrate the localization,function ,and the T4SS mechanism of recognizing and delivering virulence factors.Meanwhile,this study might find novel drug target point for clinical therapy.