炭疽芽胞杆菌氨基酸透酶BA_3317介导芽胞形成的功能及通路研究

芽胞形成起始调控对于炭疽芽胞杆菌感染宿主和在自然界中的生存非常关键，然而群体感应系统参与炭疽杆菌芽胞形成起始的研究鲜有报道。申请人团队前期研究发现炭疽芽胞杆菌氨基酸透酶BA_3317含有金黄色葡萄球菌群体感应系统成员AgrB的结构域，并且缺失后炭疽杆菌芽胞形成率显著降低。本项目将结合分子生物学和多组学手段系统研究BA_3317参与芽胞形成的功能及其通路。首先，进一步确认BA_3317在芽胞形成中发挥信号分子分泌功能；随后，利用转录组和蛋白质组发现BA_3317外分泌的信号分子参与的芽胞形成通路；最后，利用HPLC分离分析上清分泌物和芽胞形成标志物追踪分泌物中活性成分，质谱鉴定芽胞形成需要的活性成分。研究结果将阐明炭疽杆菌信号分子外分泌蛋白BA_3317功能及其参与芽胞形成通路，为炭疽杆菌芽胞形成阻断提供新靶点。

The regulation of sporulation initiation is very critical for the infection and survival in nature of Bacillus anthracis. However, there are few studies on the quorum sensing system involved in the sporulation initiation of B. anthracis. In previous research, we found that the amino acid permease BA_3317 contains the AgrB domain, the member of the Staphylococcus aureus quorum sensing system, and the sporulation efficiency of BA_3317 deletion mutant significantly reduced in B. anthracis. This project will focus on systematically study the function and pathway of BA_3317 involved in spore formation by molecular biological and multi-omics methods. First, it was further confirmed that BA_3317 play a secretory the signaling molecule role in spore formation. Further, the other members of the secreted signal proteins by the BA_3317 involved in sporulation pathways were analyzed using transcriptome and proteome. Third, the active ingredients required for spore formation was classified by HPLC, tracked by the spore formation markers, and identified by mass spectrometry. The results will elucidate the spore formation function and pathways of the secreted protein BA_3317 in B. anthracis, and provide a new target for the blocking of B. anthracis spore formation.