结核分枝杆菌（Mycobacterium tuberculosis，Mtb）属于胞内病原菌，它不仅能阻碍吞噬泡的成熟和与溶酶体的融合，还能分泌毒力因子破坏吞噬泡膜进入胞浆。吞噬泡膜的受损将诱导细胞自噬，自噬流的发生可帮助细胞清除Mtb。然而，Mtb也可分泌效应子操控细胞自噬的发生发展。尽管已知Mtb的感染能抑制细胞自噬体的形成，但对背后分子机制的研究仍了解不多。本课题组前期工作筛选出Mtb的分泌蛋白PPE16能显著抑制宿主细胞自噬体的形成，本项目希望进一步筛选鉴定出PPE16作用的宿主靶标，鉴定互作的活性中心位点，分析相互作用的化学本质，从而阐明PPE16抑制宿主细胞自噬体形成详细的分子机制。

Mycobacterium tuberculosis (Mtb), the most successful intracellular pathogenic bacterium, is not only able to hamper maturation of phagosome or fusion between phagosome and lysosome, but also able to destroy the membrane of phagosome to get access to cytoplasm by secreting virulence factor. The incompetent phagosome membrane is one kind of signal for initiation of autophagy flow, which is capable of clearing intracellular Mtb. However, Mtb has the ability to modulate the initiation and development of autophagy in host cell depending on a series of secretory effectors. Although, it is known that the infection of Mtb inhibits autophagosome formation in host cell, our knowledge about the molecular mechanism behind it is still not enough. PPE16, secreted by Mtb, was screened and identified to inhibit autophagosome formation remarkably in the previous study in our lab. In this program, we intend to further screen and identify the target of PPE16 in host cell, and identified the activity centre for this interaction, analyzing the chemical basis of the interaction, to elucidate the molecular mechanism for the inhibition effect of PPE16 on autophagosome formation in host cell.