Invasion and intracellular replication of Salmonella Typhimurium in epithelial cells

伤寒沙门氏菌(鼠伤寒沙门氏菌)是人和牛小肠结肠炎的常见病因，但在易感小鼠中会引起系统性伤寒样疾病。这种兼性细胞内病原体侵袭非吞噬细胞，特别是肠上皮细胞。我们发现，顺畅的游泳有助于肠道上皮细胞的有效入侵。化学受体MCPc与T3SS1共表达，T3SS1是有效侵袭所必需的。细胞内复制发生在SCV内和胞浆内，细菌在这两个细胞内生态位内的生长速度和转录状态非常不同。特别是，T3SS1在胞质细菌中具有功能活性，而T3SS2在液泡细菌中具有功能活性。因此，每个T3SS系统在细胞内环境中都是功能的，尽管在不同的利基环境中。此前，我们已经开发了一种环境自溶菌株，即在哺乳动物细胞的胞浆中溶解，以研究胞浆种群的作用。我们现在正在开发更多的自溶菌株和环境传感器，可以提供哺乳动物肠道中特定沙门氏菌亚群的信息。我们还在研究感染的上皮细胞中的信号通路，试图剖析特定细菌效应蛋白的作用。

Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a common cause of enterocolitis in humans and cattle but causes a systemic, typhoid-like, disease in susceptible mice. This facultative intracellular pathogen invades non-phagocytic cells, particularly intestinal epithelial cells. We have found that efficient invasion of intestinal epithelial cells is facilitated by smooth swimming. A chemoreceptor, McpC, is co-expressed with T3SS1 which is required for efficient invasion. Intracellular replication occurs within the SCV and within the cytosol, bacterial growth rates and transcriptional status within these two intracellular niches are quite different. In particular, the T3SS1 is functionally active in the cytosolic bacteria whereas the T3SS2 is functionally active in the vacuolar bacteria. Thus, each of the T3SS systems are functional in the intracellular environment albeit in different niches. Previously we have developed an environmental autolytic strain, that lysis in the cytosol of mammalian cells, to study the role of the cytosolic population. We are now developing additional autolytic strains and environmental sensors that can provide information about specific sub populations of Salmonella in the mammalian gut. We are also looking at signaling pathways in infected epithelial cells to try to dissect the roles of specific bacterial effector proteins.