Impact of ileal content on S typhimurium pathogenesis

描述（由申请方提供）：沙门氏菌是美国致死性食源性疾病的最常见原因。沙门氏菌持续污染美国食品供应的能力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，从而代表人类沙门氏菌的重要来源。本建议的第一个具体目标是评估肠道中影响S。鼠伤寒沙门氏菌基因表达采用小牛结扎回肠袢模型和S.鼠伤寒微阵列将用于评估S.鼠伤寒沙门氏菌基因表达对肠道环境的反应。第二个具体目标是评估转录后调控在S。通过测量与第一个特定目的中鉴定的调节途径相关的蛋白质水平，测定肠中鼠伤寒沙门氏菌基因表达。第三个具体目标是评估肠腔和上皮细胞的条件改变S的毒力和持久性的分子机制。鼠伤寒沙门氏菌在小肠结肠炎的小牛模型。这些实验将为肠道中沙门氏菌的需求提供新的见解，并可能为保护人类健康提供潜在的创新方法。劳汉医生完成了她的DVM 1997年5月在德克萨斯A&M大学兽医学院。她完成了博士学位。在克雷格阿尔捷博士的实验室，确定肠道短链脂肪酸对沙门氏菌入侵基因调控的影响。Lawhon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。B博士与umler在得克萨斯州A&M健康科学中心和博士亚当斯在兽医学院提供了一个独特的机会，以实现这一职业目标。

DESCRIPTION (provided by applicant): Salmonella is the most common cause of foodborne illness with lethal outcome in the US. The ability of Salmonella to consistently contaminate the US food supply creates an urgent need for better understanding of the molecular mechanism that allow this pathogen to persist successfully in food producing animals thus representing a significant source of Salmonella for humans. The first specific aim of this proposal is to evaluate the role of factors present in the intestinal tract that affect S. typhimurium gene expression. The calf ligated ileal loop model and a S. typhimurium microarray will be used to evaluate alterations in S. typhimurium gene expression in response to the intestinal envrionment. The second specific aim is to evaluate the role of post-transcriptional regulation in S. typhimurium gene expression in the intestine by measuring the levels of proteins associated with regulatory pathways identified in the first specific aim. The third specific aim is to evaluate the molecular mechanisms by which the conditions of the intestinal lumen and epithelium alter the virulence and persistence of S. typhimurium in the calf model of enterocolitis. These experiments will offer new insight into the requirements of Salmonella in the intestinal tract and may offer potential innovative approaches to safeguard human health. Dr. Lawhon completed her D.V.M. at Texas A&M University College of Veterinary Medicine in May 1997. She completed her Ph.D. in the laboratory of Dr. Craig Altier, identifying the effect of intestinal short-chain fatty acids on Salmonella invasion gene regulation. Having a strong interest in bacterial pathogenesis and in veterinary medicine, Dr. Lawhon's career goal is to become an independent investigator at the interface between these two areas. The research collaboration between Dr. Bumler 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.