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）：弯曲杆菌的空肠是美国严重细菌胃肠炎的主要原因，并已被NIH归类为粮食传播的B类生物恐怖剂。除了严重的胃肠炎引起的巨大疾病负担（在美国> 240万例）外，空肠梭菌感染还与Guillain-Barre综合征的发展高度相关，这是一种急性运动瘫痪，这是一种急性运动，这可能是由于针对Jejuni抗原的自身免疫抗体引起的。家禽植物普遍存在，无疑是用空肠梭菌定殖的，而jejuni向人类传播的最可能的途径可能是通过食用受污染的家禽肉的消费。在其自然栖息地中，空肠梭状芽孢杆菌能够在两个不同的温度（42C（鸡的核心温度）和37C（人类））下繁衍生息。因此，可能会调节空肠梭菌蛋白的温度调节，以促进适合当前环境（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，我们有证据表明发生这种温度调节。此外，空肠梭状芽胞杆菌的温度调节可能会增加37C蛋白质的表达，这在人类疾病过程中可能很重要，并且似乎定义了允许同时调节许多空肠蛋白酶蛋白的全球调节网络。现在，我们提出进一步研究空肠梭状芽孢杆菌的温度调节，重点是在37C时诱导的蛋白质，并且可能使J. Jejuni引起人类疾病所必需的蛋白质。我们将使用以下3个特定目的实现这些目标：特定目标1。使用蛋白质组学和微阵列，识别和定位在37C处诱导的Jejuni蛋白，并检查37C诱导的蛋白质的应变变异性。具体目的2。表征在37C时诱导的空肠梭状芽胞杆菌蛋白的功能和调节。特异性目标3。阐明了特异性37C诱导的蛋白在人体上皮细胞结合和体外浸润中的作用，在小鼠模型中的结肠中的作用。