Host Cell Responses To Salmonella Enterica Serovar Typhi

宿主细胞对肠沙门氏菌伤寒血清型的反应

• 批准号: 6669972
• 负责人: Olivia Steele-Mortimer
• 金额: --
• 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/6669972
• 关键词: SDS polyacrylamide gel electrophoresis; Salmonella typhimurium; apoptosis; bacteria infection mechanism; biological signal transduction; cell biology; cellular immunity; confocal scanning microscopy; gastroenteritis; gene expression; host organism interaction; molecular cloning; pathologic process; protein kinase; tissue /cell culture; western blottings

monella enterica serovar Typhimurium is a common cause of gastroenteritis. Virulence is determined by five Salmonella Pathogenicity Islands (SPI) encoded on the bacterial chromosome. SPI1 and SPI2 encode the structural components of two Type Three Secretion Sytems (TTSS) that translocate effectors into the host cell. The SPI1 effector SigD is an inositol phosphatase that induces the activation of Akt/PKB a mammalian serine threonine kinase. The role of Akt activation in pathogenesis remains unclear, however, in cultured epithelial cells it appears to be involved in preventing the onset of apoptosis in infected cells. More specifically we have found that a sigD deletion mutant induces Caspase 3 activation compared to wild type. This may be important for the survival and replication of intracellular bacteria. In macrophages activation of Akt by Salmonella is more complex since lipopolysaccharide will activate the kinase in the absence of SigD. Comparison of the two pathways has revealed important differences. In particular, SigD-mediated activation is insensitive to Wortmannin a well described inhibitor of Akt activation via phosphatidylinositol-3-kinase. Thus SigD-dependent Akt activation appears to occur via a novel pathway.

伤寒沙门氏菌是肠胃炎的常见病因。毒力是由细菌染色体上编码的5个沙门氏菌致病性岛（SPI）决定的。SPI1和SPI2编码两种第三型分泌系统（TTSS）的结构成分，将效应物转运到宿主细胞中。SPI1效应物SigD是一种肌醇磷酸酶，可诱导Akt/PKB（哺乳动物丝氨酸苏氨酸激酶）的激活。Akt激活在发病机制中的作用尚不清楚，然而，在培养的上皮细胞中，它似乎参与了防止感染细胞凋亡的发生。更具体地说，我们发现与野生型相比，sigD缺失突变体诱导Caspase 3激活。这可能对细胞内细菌的生存和复制很重要。在巨噬细胞中，沙门氏菌对Akt的激活更为复杂，因为脂多糖会在缺乏SigD的情况下激活激酶。两种通路的比较揭示了重要的差异。特别是sigd介导的激活对Wortmannin不敏感，Wortmannin是一种通过磷脂酰肌醇-3激酶激活Akt的良好抑制剂。因此，sigd依赖性Akt激活似乎是通过一种新的途径发生的。