Campylobacter jejuni proteins induced at 37C

37°C 诱导空肠弯曲菌蛋白

基本信息

批准号：
7173446
负责人：
STUART A THOMPSON
金额：
$ 30.51万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2009-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Campylobacter jejuni is the leading cause of severe bacterial gastroenteritis in the U.S., and has been classified as a food-borne Category B Bioterrorism agent by the NIH. In addition to the tremendous burden of disease due to severe gastroenteritis (>2.4 million cases/yr, in the U.S.), C. jejuni infection is highly associated with the development of Guillain-Barre syndrome, an acute motor paralysis that may result from autoimmune antibodies against C. jejuni antigens. Poultry flocks are ubiquitously and asymptomatically colonized with C. jejuni, and the most probable route of transmission of C. jejuni to humans is probably via consumption of contaminated poultry meat. In its natural habitats, C. jejuni is able to thrive at two different temperatures, 42C (the core temperature of chickens) and 37C (in humans). Consequently, there is likely to be temperature regulation of C. jejuni proteins to facilitate the optimal expression of the subset of proteins appropriate for its current environment (i.e., poultry or humans). Using complementary microarray and proteomics approaches, we have evidence that such temperature regulation occurs. Furthermore, C. jejuni temperature regulation may increase the expression at 37C of proteins that may be important in the course of human disease, and appear to define global regulatory networks that allow the simultaneous regulation of many C. jejuni proteins. We now propose further study of temperature regulation in C. jejuni, focusing on those proteins that are induced at 37C and which may be required for C. jejuni to cause disease in humans. We will achieve these goals using the following 3 specific aims: Specific Aim 1. Using proteomics and microarray, identify and localize C. jejuni proteins that are induced at 37C, and examine interstrain variability in 37C-induced proteins. Specific Aim 2. Characterize the functions and regulation of C. jejuni proteins that are induced at 37C.Specific Aim 3. Elucidate the roles of specific 37C-induced proteins in human epithelial cell binding and invasion in vitro, and in colonization in a mouse model.

描述（由申请人提供）：空肠弯曲杆菌是美国严重细菌性胃肠炎的主要原因，已被 NIH 列为食源性 B 类生物恐怖主义制剂。除了严重胃肠炎造成的巨大疾病负担（美国每年>240万例）之外，空肠弯曲菌感染还与格林-巴利综合征的发生密切相关，格林-巴利综合征是一种可能由自身免疫性疾病引起的急性运动麻痹。针对空肠弯曲菌抗原的抗体。空肠弯曲菌无处不在且无症状地定植于家禽群中，空肠弯曲菌向人类传播的最可能途径可能是通过食用受污染的家禽肉。在自然栖息地，空肠弯曲菌能够在两种不同的温度下茁壮成长：42 摄氏度（鸡的核心温度）和 37 摄氏度（人类）。因此，空肠弯曲菌蛋白质可能存在温度调节，以促进适合其当前环境（即家禽或人类）的蛋白质子集的最佳表达。使用互补的微阵列和蛋白质组学方法，我们有证据表明存在这种温度调节。此外，空肠弯曲菌温度调节可能会增加在人类疾病过程中可能重要的蛋白质在 37°C 的表达，并且似乎定义了允许同时调节许多空肠弯曲菌蛋白质的全局调节网络。我们现在建议进一步研究空肠弯曲菌的温度调节，重点关注那些在 37°C 诱导的蛋白质，这些蛋白质可能是空肠弯曲菌引起人类疾病所必需的。我们将通过以下 3 个具体目标来实现这些目标：具体目标 1. 使用蛋白质组学和微阵列，识别和定位在 37C 诱导的空肠弯曲菌蛋白，并检查 37C 诱导蛋白的株间变异性。具体目标 2. 表征 37C 诱导的空肠弯曲菌蛋白的功能和调节。具体目标 3. 阐明特定 37C 诱导蛋白在体外人上皮细胞结合和侵袭以及小鼠模型定植中的作用。