S. typhimurium Genes Required for Colonization of Cattle

描述（由申请人提供）：S。在美国，鼠伤寒是导致致命性食源性疾病的最常见原因。S.鼠伤寒沙门氏菌持续污染我们的食品供应，迫切需要更好地了解这种病原体在食品生产动物中成功持续存在的分子机制。流行病学监测结果表明，家鸽适应了沙门氏菌。引起鸽致死性副伤寒的鼠伤寒变种（噬菌体类型DT 2和DT 99）在牛中不持续存在。这项计划的目的是确定基因的流行病学成功的S。typhimurium.in牛通过基因组比较，并使用小肠结肠炎小牛模型表征其功能。本建议的第一个具体目标是评估S.在小牛中适应鸽子的鼠伤寒变种。小牛结扎回肠袢模型将用于评价鸽子变体在小牛小肠中引起液体蓄积、炎症和组织损伤的能力，并将使用经口感染模型研究小牛中的持久性。该建议的第二个具体目标是鉴定存在于S.鼠伤寒沙门氏菌菌株LT 2，但在鸽分离株中不存在。为了鉴定牛分离株特有的LT 2特异性基因，我们将通过Southern印迹法在大量鼠伤寒沙门氏菌分离株中建立流行病学相关性。这项建议的最终具体目标是测试从S.鼠伤寒沙门氏菌牛变异体改变鸽适应性沙门氏菌宿主特异性的能力。鼠伤寒分离株。 博士Andrews-Polymenis完成了博士学位。在Ralph Isberg博士的实验室中，确定了嗜肺军团菌细胞内生长所必需的新因子。她完成了她的D.V.M. 2001年5月以优异成绩在德克萨斯A&M大学兽医学院毕业。Andrews-Polymenis博士对细菌发病机理和兽医学有着浓厚的兴趣，他的职业目标是成为这两个领域之间的独立研究者。 Baumler博士在德克萨斯A&M健康科学中心和亚当斯博士在兽医学院的研究合作为实现这一职业目标提供了一个独特的机会。

DESCRIPTION (provided by applicant): S. typhimurium is the most common cause of foodborne illness with lethal outcome in the US. The ability of S. typhimurium to consistently contaminate our food supply, creates an urgent need for better understanding of the molecular mechanisms that allow this pathogen to persist successfully in food producing animals. Epidemiological surveillance strongly suggests that pigeon adapted S. typhimurium variants (phage types DT2 and DT99) that cause fatal pigeon paratyphoid do not persist in cattle. The objective of this proposal is to identify the genes responsible for the epidemiologic success of S. typhimurium.in cattle through genomic comparison and characterize their function using the calf model of enterocolitis. The first specific aim of this proposal is to evaluate the virulence and persistence of S. typhimurium pigeon adapted variants in calves. The calf ligated ileal loop model will be used to evaluate the ability of pigeon variants to cause fluid accumulation, inflammation and tissue damage in the calf small intestine, and persistence in calves will be studied using oral models of infection. The second specific aim of this proposal is to identify genes present in S. typhimurium strain LT2 but absent from pigeon isolates. To identify LT2 specific genes unique to cattle isolates we will establish a epidemiological correlation within a large number of S.typhimurium isolates by southern blotting. The final specific aim of this proposal is to test unique regions of DNA isolated from S. typhimurium cattle variants for the ability to alter host specificity of pigeon adapted S. typhimurium isolates. Dr. Andrews-Polymenis completed her Ph.D. in the laboratory of Dr. Ralph Isberg, identifying novel factors necessary for intracellular growth of Legionella pneumophila. She completed her D.V.M. cum laude at Texas A&M University College of Veterinary Medicine in May 2001. Having a strong interest in bacterial pathogenesis and in veterinary medicine, Dr. Andrews-Polymenis' career goal is to become an independent investigator at the interface between these two areas. The research collaboration between Dr. Baumler in the Texas A&M Health Science Center and Dr. Adams in the College of Veterinary Medicine provides a unique opportunity to achieve this career goal.