Impact of ileal content on S typhimurium pathogenesis

描述（由申请人提供）：沙门氏菌是美国食源性疾病最常见的致命原因。沙门氏菌持续污染美国食品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，从而代表了人类沙门氏菌的重要来源。本提案的第一个具体目的是评估肠道中存在的影响鼠伤寒沙门氏菌基因表达的因素的作用。犊牛结扎回肠环模型和鼠伤寒沙门氏菌微阵列将用于评估鼠伤寒沙门氏菌基因表达对肠道环境的响应。第二个特定目的是通过测量在第一个特定目的中发现的与调节途径相关的蛋白质水平，评估转录后调控在肠内鼠伤寒沙门氏菌基因表达中的作用。第三个具体目的是评估在小牛小肠结肠炎模型中，肠腔和上皮条件改变鼠伤寒沙门氏菌毒力和持久性的分子机制。这些实验将对肠道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。1997年5月，她在德州农工大学兽医学院获得兽医博士学位。她在克雷格·阿尔蒂埃（Craig Altier）博士的实验室完成了博士学位，研究方向是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之间的独立研究者。德克萨斯A&M健康科学中心的B博士umler和兽医学院的Adams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): 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.