Invasion and formation of the Salmonella-Containing Vacuole

含有沙门氏菌的液泡的侵袭和形成

• 批准号: 8745395
• 负责人: Olivia Steele-Mortimer
• 金额: $ 59.94万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745395
• 关键词: Bacteria; Biogenesis; Biological Models; Canis familiaris; Cattle; Cell Line; Cells; Colon; Disease; Enterocolitis; Environment; Epithelial Cells; Goals; Hela Cells; Human; Invaded; Kidney; Lysosomes; MDCK cell; Molecular; Mus; Pathway interactions; Phagosomes; Proteins; Salmonella; Salmonella enterica; Staging; System; Type III Secretion System Pathway; Typhoid Fever; Vacuole; Virulence Factors; cohort; in vitro Model; intestinal epithelium; late endosome; monolayer; pathogen

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, and survives within a modified phagosome known as the Salmonella-containing vacuoles (SCV). Two type III secretion systems (T3SS), which translocate distinct cohorts of bacterial effector proteins into the host cell, are required for establishment of the intracellular replicative environment. Invasion is dependent on T3SS1 whereas T3SS2 is induced intracellularly and is associated with intracellular survival/replication and biogenesis of the SCV. A very important aspect of the host-pathogen interaction is the biogenesis of the SCV, from initial formation through to the ultimate release of bacteria. We have previously shown that SCV biogenesis involves sustained dynamic interactions with the endocytic pathway including late endosomes and lysosome. These studies were done using HeLa cells, which have been widely used in the field. However, one of our goals is to developing more physiologically relevant model systems. Therefore, we are using epithelial cell lines, such as MDCK cells (canine kidney) and C2Bbe1 (human colon), which can form polarized monolayers. We are focusing our efforts on the initial stages of SCV formation, including ruffle formation and SCV biogenesis.

鼠伤寒沙门氏菌（S.鼠伤寒沙门氏菌（Typhimurium）是人类和牛小肠结肠炎的常见病因，但在易感小鼠中会引起全身性伤寒样疾病。这种兼性细胞内病原体侵入非吞噬细胞，例如在肠上皮中发现的那些细胞，并在被称为含沙门氏菌空泡（SCV）的修饰的吞噬体内存活。两种III型分泌系统（T3 SS），其将不同的细菌效应蛋白质组易位到宿主细胞中，是建立细胞内复制环境所必需的。侵袭依赖于T3 SS 1，而T3 SS 2是在细胞内诱导的，并且与SCV的细胞内存活/复制和生物发生相关。宿主-病原体相互作用的一个非常重要的方面是SCV的生物发生，从细菌的初始形成到最终释放。我们以前已经表明，SCV的生物发生涉及持续的动态相互作用与内吞途径，包括晚期内体和溶酶体。这些研究是使用在该领域广泛使用的HeLa细胞进行的。然而，我们的目标之一是开发更多的生理相关的模型系统。因此，我们正在使用上皮细胞系，如MDCK细胞（犬肾）和C2Bbe 1（人结肠），它们可以形成极化单层。 我们正集中精力研究SCV形成的初始阶段，包括皱褶形成和SCV生物发生。