S. typhimurium Genes Required for Colonization of Cattle

描述（由申请人提供）：在美国，鼠伤寒沙门氏菌是食源性疾病最常见的致死性原因。鼠伤寒沙门氏菌持续污染我们的食物供应的能力，使我们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。流行病学监测有力地表明，导致致命鸽子副伤寒的鸽子适应鼠伤寒沙门氏菌变种（噬菌体型DT2和DT99）不会在牛中持续存在。本提案的目的是确定负责鼠伤寒沙门氏菌流行病学成功的基因。在牛通过基因组比较和表征其功能使用小牛小肠结肠炎模型。本建议的第一个具体目的是评估鼠伤寒沙门氏菌鸽子适应变种在小牛中的毒力和持久性。犊牛结扎回肠环模型将用于评估鸽子变异引起犊牛小肠液体积聚、炎症和组织损伤的能力，并将通过口腔感染模型研究犊牛的持续性。本提案的第二个具体目的是鉴定鼠伤寒沙门氏菌菌株LT2中存在但鸽子分离株中不存在的基因。为了鉴定牛分离株特有的LT2特异性基因，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。本提案的最后一个具体目的是测试从鼠伤寒沙门氏菌牛变种中分离的DNA的独特区域，以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。

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.