PATHOGENESIS OF SALMONELLA DUBLIN INTESTINAL INFECTIONS

都柏林沙门氏菌肠道感染的发病机制

• 批准号: 6238882
• 负责人: Joshua Fierer
• 金额: $ 13.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6238882
• 关键词: Escherichia coli; Salmonella; Salmonella infections; antibody receptor; bactericidal immunity; complement pathway; complement receptor; fusion gene; gastrointestinal infection; gene expression; genetic regulation; host organism interaction; interferon gamma; laboratory mouse; macrophage; pathologic process; site directed mutagenesis; tissue /cell culture; tumor necrosis factor alpha; virulence

Salmonella serovars are important causes of gastroenteritis and systemic disease worldwide. Non-typhoid Salmonella serovars associated with septicemia in people contain virulence plasmids encoding genes that promote dissemination of infection from the gastrointestinal tract. Virulence plasmids of S. typhimurium and S. dublin carry genes that increase resistance of the bacteria to both humoral and cellular components of the host defense. The rck gene encodes high level resistance to complement mediated killing, while the spv locus appears to enhance the ability of Salmonella to grow within cells of the reticuloendothelial system. The central theme of this Unit is that the plasmid-mediated virulence factors are expressed as specific responses to interactions between the bacteria and key components of the host defense system that operate in the intestine: complement, epithelial cells, macrophages, and gammadelta T cells. Specific bacterial control mechanisms are postulated to regulate rck and spv expression in response to environmental conditions in vivo. In addition, the host antibody response is postulated to down-regulate bacterial spv expression inside macrophages by a novel receptor-mediated mechanism. The Specific Aims are: 1) to determine the conditions which regulate expression of the plasmid-mediated complement resistance locus rck; 2) to define the molecular domains of Rck involved in complement resistance, and the interaction of Rck with complement components; 3) to determine the role of rck in complement resistance and virulence of wild-type strains; 4) to define host conditions that regulate expression of the plasmid- mediated virulence operon spv inside macrophages; 5) to determine whether spv genes are expressed in cultured epithelial cells; 6) to determine the role of gammadelta T cells in host resistance to Salmonella dublin strains with and without the spv locus. These studies follow closely the overall objective of the Program to characterize the role of intestinal host-environment interactions in host defense and the pathogenesis of disease.

沙门氏菌血清型是胃肠炎和全身性疾病的重要原因。 全球范围内的疾病。 非伤寒沙门氏菌相关血清型 人的败血症含有编码基因的毒力质粒， 促进感染从胃肠道传播。 毒力质粒。鼠伤寒沙门氏菌和S.都柏林携带的基因 增加细菌对体液和细胞的抵抗力 主机防御的组成部分。 rck基因编码高水平的 抵抗补体介导的杀伤，而SPV基因座出现 提高沙门氏菌在细胞内生长的能力， 网状内皮系统 本单元的中心主题是， 质粒介导的毒力因子表达为特异性应答 细菌和宿主关键成分之间的相互作用 在肠道中运作的防御系统：补体，上皮细胞 细胞、巨噬细胞和γ δ T细胞。 特定细菌控制 推测其机制是调节RCK和SPV的表达 与体内环境条件的关系。 此外，宿主抗体 反应被假定为下调细菌spv表达， 巨噬细胞通过一种新的受体介导的机制。 具体目标 （1）确定调控基因表达的条件， 质粒介导的补体抗性基因座rck; 2）确定 参与补体抵抗的Rck的分子结构域， Rck与补体成分的相互作用; 3）确定Rck在补体中的作用 rck在补体抵抗和野生型菌株毒力中的作用; 4） 以确定调节质粒表达的宿主条件- 介导的巨噬细胞内的毒力操纵子spv; 5）以确定是否 spv基因在培养的上皮细胞中表达; 6）为了确定 γ δ T细胞在宿主抵抗都柏林沙门氏菌中的作用 具有和不具有SPV基因座的菌株。 这些研究密切关注 该计划的总体目标是描述肠道的作用， 宿主防御中的宿主-环境相互作用和 疾病