Functional impact of lipid logistics on mycobacterial infection in Dictyostelium (P25)

结核病（Tb）是由结核分枝杆菌（Mtb）引起的一种广泛传播的传染病。结核杆菌的一个主要特征是在慢性感染过程中形成脂质泡沫巨噬细胞，结核杆菌在此过程中通过一种新的膜接触部位从宿主中动员脂滴（ld）。在这个项目中，我们将通过Dictyostelium/Mycobacterium marine感染模型揭示分枝杆菌获取和利用宿主脂质的分子机制。为此，我们将(i)在亚细胞和超微结构水平上揭示分枝杆菌和宿主之间的代谢脂质流动，（ii）分析病原体诱导的膜接触位点（MCSs）的形成，作为专门从事细胞器间脂质运输的微室，以确定宿主到病原体的脂质流动在分枝杆菌感染中的作用。因此，我们的工作将揭示细胞内分枝杆菌在感染期间利用宿主脂质的新途径。

Tuberculosis (Tb) is a wide-spread infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb). A main characteristic of Tb is the formation of lipid-loaded, foamy macrophages during chronic infection, and Mtb mobilizes in this process lipid droplets (LDs) from their host via a novel membrane contact site. In this project, we will unravel the molecular mechanisms by which mycobacteria acquire and exploit host lipids using the Dictyostelium/Mycobacterium marinum infection model. For this, we will (i) unravel the metabolic lipid flows between mycobacteria and their host at the subcellular and ultrastructural level, and (ii) analyze the formation of pathogen-induced membrane contact sites (MCSs) as microcompartments specialized in interorganellar lipid transport to determine the role of host-to-pathogen lipid flow in mycobacterial infection. Our work will thus uncover a novel pathway by which intracellular mycobacteria exploit host lipids during infection.