Invasion and intracellular replication of Salmonella Typhimurium in epithelial cells

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一种系统性的伤寒样疾病。这种兼性的细胞内病原体侵入非吞噬细胞，如肠上皮中的细胞。在内化之后，细菌被定位在一个修改的吞噬小体中，被称为含有沙门氏菌的空泡(SCV)。在上皮细胞中，细胞内复制发生在两个不同的生态位内，即SCV和胞浆，其中细菌的生长速度和转录活性不同。与上皮细胞的相互作用在很大程度上是由两个III型分泌系统(T3SS1和T3SS2)介导的，它们将不同的细菌效应蛋白序列转移到宿主细胞中。侵袭依赖于T3SS1，而T3SS2是在细胞内诱导的，并与SCV的生物发生和空泡内的生存/复制有关。最近，我们一直在研究上皮细胞中空泡复制和胞浆复制的相对重要性。在大约5%-20%的感染细胞中，鼠伤寒沙门氏菌从液泡中逃逸，并在胞浆中存活和复制。我们发现，在以后的时间点上，T3SS1在胞质细菌中具有功能活性，而T3SS2仅在空泡细菌中具有功能活性。

Salmonella enterica serovar Typhimurium (S. 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, such as those found in the intestinal epithelium. Following internalization the bacteria are localized within a modified phagosome, known as the Salmonella-containing vacuoles (SCV). In epithelial cells, intracellular replication occurs within two distinct niches, the SCV and the cytosol, within which the bacterial growth rates and transcriptional activities differ. Interactions with epithelial cells are largely mediated by two type III secretion systems (T3SS1 and T3SS2), which translocate distinct cohorts of bacterial effector proteins into the host cell. Invasion is dependent on T3SS1 whereas T3SS2 is induced intracellularly and is associated with biogenesis of the SCV and intravacuolar survival/replication. Recently we have been investigating the relative importance of vacuolar versus cytosolic replication in epithelial cells. In approximately 5-20% of infected cells S. Typhimurium escape from the vacuole and survive and replicate in the cytosol. We have found that at later time points the T3SS1 is functionally active in the cytosolic bacteria whereas the T3SS2 is functionally active only in the vacuolar bacteria.