Salmonella-Host Cell Interactions

鼠伤寒沙门氏菌是引起人类小肠结肠炎的最常见原因之一。这种兼性细胞内病原体的发病机制依赖于侵袭非吞噬细胞的能力，如肠上皮中发现的那些细胞。侵袭依赖于III型分泌系统(T3SS1)，该系统用于将一组细菌效应蛋白转移到宿主细胞中。沙门氏菌在细胞内内化后，在一个修饰的吞噬小体--含沙门氏菌空泡(SCV)内存活和复制。第二个III型系统(T3SS2)是在细胞内诱导的，与SCV的细胞内生存/复制和生物发生有关。为了了解沙门氏菌的致病机制，我们必须剖析单独的T3SS1和T3SS2效应蛋白的作用，以及控制它们在宿主细胞内表达和活性的机制。由于这些毒力因子的表达和功能高度依赖于细胞内环境，我们正致力于开发合适的体外系统，在分子水平上研究它们的活性。

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.