结核病是威胁人类健康的重大传染病，其病原体结核杆菌特异的PE/PPE家族与细菌的感染和致病密切相关。我们前期研究报道PPE家族蛋白PPE57可以调节宿主免疫反应，是结核病诊断和疫苗研发的潜在优良抗原，进一步研究发现PPE57增加重组耻垢杆菌细胞壁脂质TDM的含量，并可能与TMM（TDM的前体物）的转运蛋白MmpL3相互作用。但在结核杆菌中，PPE57的生物学功能未知。本项目我们利用结核杆菌PPE57敲除株和回复株，从细菌菌体和细菌感染宿主两方面展开。在细菌层面，研究PPE57对结核杆菌细胞壁TDM的作用，并探讨PPE57协同MmpL3影响TMM转运的分子机制；在结核杆菌感染宿主层面，阐明PPE57调控巨噬细胞脂滴形成，抑制细胞自噬，并导致胞内细菌持留的作用和机制。研究结果将揭示PPE57在结核杆菌脂质转运及感染中发挥的作用，为全面阐明PPE家族蛋白的功能及结核杆菌感染和致病机制奠定基础。

Tuberculosis is a major infectious disease threatening human health. The specific gene family PE/PPE of Mycobacterium tuberculosis is closely related to bacterial infection and pathogenesis. Our previous study reported that PPE family protein PPE57 can regulate host immune response, and is a potential good antigen for TB diagnosis and vaccine development. Further study found that PPE57 increased the content of TDM in recombinant Mycobacterium smegmatis cell wall lipids, and may interact with the transporter MmpL3 of TMM (the precursor of TDM). However, the biological function of PPE57 in the pathogenic Mtb was unknown. This project will be carried out from both bacterial and host infections. At the bacterial level, the effects of PPE57 on TDM of Mtb cell wall lipids will be studied, and the molecular mechanism of PPE57 and MmpL3 affecting TMM transport will be discoveried. At the level of host infection by Mtb, the effects and mechanisms of PPE57 on regulating the formation of lipid droplets in macrophages, inhibiting autophagy, and causing intracellular bacterial persistence will be clarified. The study will reveal the role of PPE57 in the lipid transport and infection of Mtb, and lay a foundation for the comprehensive explanation of the function of PPE family proteins and the pathogenesis of Mtb infection.