猪链球菌2型内皮素转化酶的致病机制研究

Streptococcus suis serotype 2 (S. suis 2) is an important pathogen jeopardizing the development of the pig industry in our country. Inflammation mediated by polymorphonuclear neutrophil (PMN) plays an important role in the pathogenesis of S. suis infection. Therefore, further study on the interaction mechanism between S. suis and PMN is meaningful. In our recent study, S. suis endothelin converting enzyme (SsEce) was verified to be associated with pathogenicity and have the capacity to convert big endothelin-1 (precursor of endothelin-1) into mature endothelin-1. As reported, endothelin-1 is capable to promote PMN recruitment and activation. These imply that SsEce interacts with PMN during infection process, mediating the pathogenicity of S. suis. In this project, the role of SsEce in S. suis pathogenesis will be revealed from three levels as follows: (1) Express the SsEce protein and analyze its function to activate endthelin at protein level; (2) Construct ssEce mutant and complement strains, and analyze the impact of SsEce on PMN recruitment and activation at cellular level; (3) Clarify the role of SsEce on PMN recruitment and S. suis 2 pathogenesis during infection in vivo. This study lays the foundation for the revealing of interaction between S. suis and PMN, and deep elucidation of the molecular pathogenesis of S. suis 2, which provides an important scientific basis for developing relative methods to prevent and treat S. suis 2 infection.

猪链球菌2型是当前严重危害我国养猪业健康发展的重要病原菌，而中性粒细胞介导的炎症反应在猪链球菌感染与致病中发挥重要作用，因此深入了解猪链球菌和中性粒细胞的互作机制具有重要意义。本人前期发现猪链球菌内皮素转化酶(SsEce)与致病性相关，并具有活化内皮素-1的作用，而已有研究报道内皮素-1具有促中性粒细胞募集和激活的功能，提示SsEce通过与中性粒细胞互作，进而影响猪链球菌的致病性。本项目拟从三个层次研究SsEce的致病机理：(1)表达SsEce，在蛋白水平研究SsEce活化内皮素的功能；(2)构建缺失株ΔssEce和互补菌株，在细胞水平分析SsEce对中性粒细胞募集和激活的影响；(3)在动物水平探讨SsEce对中性粒细胞募集、血管通透性和猪链球菌2型致病性的影响。以上研究将为揭示猪链球菌与中性粒细胞的互作机制和深入解析猪链球菌2型的分子致病机制奠定基础，为研发相应的防治方法提供科学依据。

猪链球菌是一种重要的人畜共患传染病病原，可经口感染，深入了解猪链球菌的致病机理具有重要意义。本人前期发现猪链球菌内皮素转化酶与致病性相关，然而其介导的致病机理并不清楚。本项目从三个层次研究该基因介导的致病机理：表达和纯化了猪链球菌内皮素转化酶，从体内和体外研究了该蛋白在猪链球菌致病过程中的作用；构建了内皮素转化酶基因缺失株和互补菌株，证明该基因参与猪链球菌对脑微血管内皮细胞和Hep2细胞的粘附入侵，以及促进中性粒细胞在脑膜炎中过度募集。在小鼠模型(体内模型)中证明猪链球菌内皮素转化酶与中性粒细胞募集、血脑屏障通透性，以及猪链球菌致病性密切相关。以上研究将为深入解析猪链球菌的分子致病机制奠定基础，为研发相应的防治方法提供科学依据。