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Determination of host response elicited by different Salmonella lifestyles

A number of mammalian cell types are susceptible to Salmonella Typhimurium infection, including epithelial cells, fibroblasts and macrophages. It has recently been demonstrated that Salmonella display specific lifestyles in a host cell type-specific manner, where these lifestyles are remarkable for the subcellular localization and replication rate of Salmonella. During epithelial cells infection, Salmonella are first uptaken by the host cell and being encapsulated in a unique endocytic compartment termed Salmonella-containing vacuole (SCV). Within the SCV, Salmonella could remodel the SCV into a viable replicative niche or rupture the SCV and hyper-replicate in the host cytosol. Salmonella replicate at distinct rates in the two localizations, the Salmonella replication in SCV commences from 5 hours post-infection (pi) and infected host cell harbors less then 10 bacteria at 8h pi. While the cytosolic Salmonella begins replication within the first hour of infection at a rate of 30 minutes per division and accumulates up to over 50 bacteria in the host at 8h pi. To understand how Salmonella achieves the two distinct intracellular lifestyles as well as the pathophysiological impacts of the two lifestyles, the primitive goal of my project is to develop a bacterial-borne fluorescent reporter that clearly depicts the subcellular localization and replication rate of Salmonella. With this multiplex fluorescent reporter, we will set to explore the fundamental biological questions: to determine the immune response of epithelial cells against the two Salmonella lifestyles.

Project status : Declined