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

结核病是由结核分枝杆菌(Mtb)引起的一种广泛传播的传染病。结核分枝杆菌的一个主要特征是在慢性感染过程中形成脂质负载的泡沫巨噬细胞，在这个过程中，结核分枝杆菌通过一个新的膜接触部位动员宿主的脂滴(LDS)。在这个项目中，我们将使用Dictyostelials/Mycotis marum感染模型来揭示分枝杆菌获取和利用宿主脂类的分子机制。为此，我们将(I)在亚细胞和超微结构水平上揭示分枝杆菌与宿主之间的代谢脂流，(Ii)分析病原体诱导的膜接触部位(MCSs)作为专门负责细胞器间脂质运输的微室的形成，以确定宿主至病原体的脂流在分枝杆菌感染中的作用。因此，我们的工作将揭示一种新的途径，通过这种途径，细胞内的分枝杆菌在感染期间利用宿主脂肪。

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.