Salmonella-Host Cell Interactions

鼠伤寒沙门氏菌是人类小肠结肠炎最常见的病因之一。这种兼性细胞内病原体的发病机制依赖于侵入非吞噬细胞的能力，例如在肠上皮中发现的那些。入侵依赖于III型分泌系统（T3 SS 1），其用于将一组细菌效应蛋白易位到宿主细胞中。在内化后，细胞内沙门氏菌存活并在修饰的吞噬体（含沙门氏菌的空泡（SCV））内复制。第二种III型系统（T3 SS 2）在细胞内诱导，并且与SCV的细胞内存活/复制和生物发生相关。为了了解沙门氏菌的发病机制，我们必须剖析T3 SS 1和T3 SS 2效应蛋白的作用，以及控制它们在宿主细胞内的表达和活性的机制。由于这些毒力因子的表达和功能非常依赖于细胞内环境，因此我们专注于开发适当的体外系统以在分子水平上研究其活性。

Salmonella enterica serovar Typhimurium is one of the most common causes of enterocolitis in humans. Pathogenesis of this facultative intracellular pathogen is dependent on the ability to invade non-phagocytic cells, such as those found in the intestinal epithelium. Invasion is dependent on a type III secretion system (T3SS1), which is used to translocate a set of bacterial effector proteins into the host cell. Following internalization intracellular Salmonella survive and replicate within a modified phagosome, the Salmonella-containing vacuole (SCV). A second type III system (T3SS2) is induced intracellularly and is associated with intracellular survival/replication and biogenesis of the SCV. To understand Salmonella pathogenesis we must dissect the roles of the individual T3SS1 and T3SS2 effector proteins as well as the mechanisms that control their expression and activity inside host cells. Since the expression and function of these virulence factors is exquisitely dependent on the intracellular environment, we are focusing on developing appropriate in vitro systems to study their activities at the molecular level.