S. typhimurium Genes Required for Colonization of Cattle

描述(由申请人提供)：鼠伤寒沙门氏菌是美国最常见的食源性疾病致死原因。鼠伤寒沙门氏菌能够持续污染我们的食物供应，迫切需要更好地了解使这种病原体在食品生产动物中成功存在的分子机制。流行病学监测强烈表明，引起致命性鸽子副伤寒的鸽子适应的鼠伤寒沙门氏菌变种(噬菌体类型DT2和DT99)在牛身上不存在。这项建议的目的是通过基因组比较确定在牛中成功流行鼠伤寒沙门氏菌的基因，并使用小牛小肠结肠炎模型来表征它们的功能。这项建议的第一个具体目标是评估鼠伤寒沙门氏菌适应变种在犊牛中的毒力和持久性。小牛结扎回肠环模型将被用来评估鸽子变体在小牛小肠中引起液体堆积、炎症和组织损伤的能力，并将使用口服感染模型来研究小牛的持久性。这项建议的第二个具体目标是识别存在于鼠伤寒沙门氏菌菌株LT2中但在鸽子分离株中缺失的基因。为了鉴定牛分离株特有的LT2基因，我们将通过Southern blotting在大量鼠伤寒沙门氏菌分离株中建立流行病学相关性。这项建议的最后一个具体目标是测试从牛鼠伤寒沙门氏菌变异株中分离出的DNA的独特区域，以了解改变鸽子适应的鼠伤寒沙门氏菌分离株的宿主特异性的能力。 Andrews-Polymenis博士在Ralph Isberg博士的实验室完成了她的博士学位，确定了嗜肺军团菌细胞内生长所必需的新因素。2001年5月，她以优异的成绩在德克萨斯农工大学兽医学院完成了医学博士学位。安德鲁斯-波尔梅尼斯博士对细菌发病机制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交界处的独立研究员。德克萨斯农工大学健康科学中心的鲍姆勒博士和兽医学院的亚当斯博士之间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.