PATHOGENESIS OF SALMONELLA DUBLIN INTESTINAL INFECTIONS

沙门氏菌血清型是引起胃肠炎和系统性肠炎的重要原因 世界范围内的疾病。与非伤寒沙门氏菌有关的血清型 人的败血症含有毒力质粒编码的基因 促进来自胃肠道的感染传播。 鼠伤寒沙门氏菌和都柏林沙门氏菌的毒力质粒携带的基因 提高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 对补体介导的杀伤产生抵抗性，同时出现SPV基因座 加强沙门氏菌在沙门氏菌细胞内的生长能力 网状内皮系统。该股的中心主题是 质粒介导的毒力因子以特异性反应的形式表达 细菌与宿主的关键成分之间的相互作用 在肠道中运行的防御系统：补体，上皮 细胞、巨噬细胞和Gammadelta T细胞。特定细菌控制 调节rck和spv表达的机制被认为是 对活体内的环境条件。此外，宿主抗体 推测反应下调细菌SPV在体内的表达 巨噬细胞通过一种新的受体介导机制。具体目标 主要有：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 RCK参与补体抵抗的分子结构域，以及 RCK与补体成分的相互作用；3)确定其作用 Rck在野生型菌株补体抗性和毒力中的作用 为了定义调节表达的宿主条件-- 巨噬细胞内介导的毒力操纵子SPV；5)确定 SPV基因在培养的上皮细胞中表达；6)确定 Gammadelta T细胞在宿主对都柏林沙门氏菌耐药中的作用 有无SPV基因座的菌株。这些研究紧跟着 该计划的总体目标是确定肠道的作用 寄主防御中的宿主-环境相互作用及其发病机制 疾病。

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.