ANALYSIS OF THE SALMONELLA TYPHIMURIUM VIRULENCE PLASMID

鼠伤寒沙门氏菌和许多其他种类的沙门氏菌是主要 美国人类发病和死亡的原因， 在全世界都有。 沙门氏菌病主要是通过 摄入受污染的肉类、奶制品和家禽产品。 因此 更好地了解沙门氏菌的致病机理将有助于 通过开发疫苗、改进治疗方法和 疾病管理和改善粮食农业方法 生产 最近，质粒酶与几种真菌的毒力有关。 沙门氏菌;然而，很少有人知道的机制或遗传学， 质粒介导的毒力 拟议研究的目标是 因此，在分子水平上确定 质粒对S.鼠伤寒。 第一特定 目的是鉴定质粒编码的毒力因子和相关基因， 鼠伤寒沙门氏菌经口扩散至小肠外 接种小鼠。 首席研究员克隆并变异了 质粒的毒力基因，这些结果是基础， 继续使用分子质粒，在解剖质粒中进行遗传分析- 介导的毒力。 毒力质粒编码的蛋白质未被检测到 由S表示，鼠伤寒沙门氏菌在体外生长，表明毒力 基因可以被调节以便仅在动物宿主中表达。 因此，最近分离的Tn 5基因。 第二个具体目标是 因此，为了阐明质粒编码的毒力基因是如何被调控的， 通过构建操纵子融合体和分析mRNA。 毒力 质粒编码的蛋白质及其在鼠伤寒沙门氏菌细胞中的位置将被 作为第三个具体目标。 这些研究是一种自然延伸 进一步描述毒力因子及其在 引发保护性免疫

Salmonella typhimurium and many other species of Salmonella are major causes of morbidity and mortality in humans in the United States and throughout the world. Salmonellosis is acquired primarily through ingestion of contaminated meat, dairy, and poultry products. Thus, a better understanding of pathogenesis of Salmonella should be useful for prevention of disease through vaccine development, improved therapy and management of disease, and improved agricultural methods for food production. Plasmids have recently been associated with virulence of several species of Salmonella; however, little is known about the mechanism or the genetics of plasmid-mediated virulence. The objectives of the proposed research are therefore to identify at the molecular level mechanism(s) by which the plasmid contributes to the virulence of S. typhimurium. The first specific aim is to identify plasmid-encoded virulence factors and genes responsible for the spread S typhimurium beyond the small intestine of orally inoculated mice. The principal investigator has cloned and mutated virulence genes of the plasmid, and these results are the basis for the continued use of molecular plasmid, genetic analysis in dissecting plasmid- mediated virulence. Virulence plasmid-encoded proteins were not detectably expressed by S,. typhimurium growing in vitro, suggesting that virulence genes may be regulated so as to be expressed only in the animal host. Therefore, recently isolated Tn5 genes. The second specific aim is therefore to elucidate how plasmid-encoded virulence genes are regulated through construction of operon fusions and analysis of mRNA. Virulence plasmid-encoded proteins and their locations in S typhimurium cells will be examined as the third specific aim. These studies are a natural extension of efforts to further characterize virulence factors and their roles in eliciting protective immunity.