分枝杆菌PPE38蛋白的致病机制研究

PE/PPE是分枝杆菌属所特有的基因家族,在结核分枝杆菌基因组中约10% 基因编码PE/PPE家族蛋白，被认为与细菌抗原变异有关，在细菌免疫逃逸中起重要作用，但至今对其作用的分子机制所知有限。我们前期研究发现，PPE38蛋白在诱导炎性因子的分泌、引起巨噬细胞坏死、维持肉芽肿结构等方面起重要作用。本研究将验证PPE38蛋白与宿主特异受体结合，影响宿主相关信号通路，导致细胞坏死和细菌在组织间播散的科学假设。鉴定宿主与PPE38蛋白相互作用的受体；研究PPE38引发的下游信号通路，阐明引起炎性因子分泌和细胞坏死的分子机制；利用基因芯片技术筛选与肉芽肿形成及维持相关基因及其调控网络，通过斑马鱼基因敲除技术验证关键基因的功能，明确其维持肉芽肿结构的分子机制。本研究成果将有助于阐明PE/PPE家族蛋白在分枝杆菌致病中的重要作用，而且对研究其他细胞壁蛋白与宿主的相互作用有很好的借鉴作用。

PE / PPE family is characteristic of mycobacterium, genes of PE / PPE family account for about 10% of the entire Mycobacterium tuberculosis genome, may related to antigenic variation, and can regulate the host immune response. Our previous study found that M. marinum PPE38 protein is able to induce the secretion of pro-inflammatory factors , cause the necrosis of macrophages and play an important role in granuloma development. We are going to investigate how PPE38 protein interacts with host receptors, activate multiple intracellular signaling pathways, promote cell necrosis and the spread of bacteria between the tissue. We will also apply zebrafish infection model to study the function of key genes and pathogenic mechanism. The results of this study will clarify the function of PPE protein in mycobacterial pathogenesis, and provide valuable information for investigating the interaction between cell wall protein and host.