Invasion and intracellular replication of Salmonella Typhimurium in epithelial cells

鼠伤寒沙门氏菌对上皮细胞的侵袭和细胞内复制

• 批准号: 9560558
• 负责人: Olivia Steele-Mortimer
• 金额: $ 53.59万
• 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/9560558
• 关键词: Bacteria; Biogenesis; Biological Models; Cattle; Cells; Cytosol; Disease; Enterocolitis; Environment; Epithelial Cells; Genetic Transcription; Goals; Growth; Human; Invaded; Mediating; Molecular; Mus; Pathway interactions; Phagosomes; Proteins; Salmonella; Salmonella enterica; Salmonella typhimurium; System; Time; Type III Secretion System Pathway; Typhoid Fever; Vacuole; Virulence Factors; cohort; in vitro Model; intestinal epithelium; 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. 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.

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。在内化之后，细菌定位在被称为含沙门氏菌的空泡（SCV）的修饰的吞噬体内。在上皮细胞中，细胞内复制发生在两个不同的小生境中，SCV和胞质溶胶，其中细菌生长速率和转录活性不同。与上皮细胞的相互作用主要由两种III型分泌系统（T3 SS 1和T3 SS 2）介导，其将细菌效应蛋白的不同群组转运到宿主细胞中。侵袭依赖于T3 SS 1，而T3 SS 2是在细胞内诱导的，并且与SCV的生物发生和液泡内存活/复制相关。最近，我们一直在研究上皮细胞中空泡复制与胞质复制的相对重要性。在约5-20%的感染细胞中，S.鼠伤寒沙门氏菌从空泡中逃逸，在胞质中存活和复制。我们发现，在稍后的时间点，T3 SS 1在胞质细菌中具有功能活性，而T3 SS 2仅在液泡细菌中具有功能活性。