Campylobacter jejuni proteins induced at 37C

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，并已被NIH列为食源性B类生物恐怖剂。除了严重胃肠炎造成的巨大疾病负担（在美国，> 240万例/年），C.空肠感染与格林-巴利综合征的发展高度相关，格林-巴利综合征是一种急性运动麻痹，可能由抗C.空肠抗原家禽群中普遍存在且无症状的C. jejuni，C.空肠感染人类可能是通过食用受污染的禽肉。在其自然栖息地，C.空肠能够在两种不同的温度下茁壮成长，42 ℃（鸡的核心温度）和37 ℃（人类）。因此，可能存在C的温度调节。空肠蛋白以促进适合于其当前环境的蛋白质子集的最佳表达（即，家禽或人类）。使用互补的微阵列和蛋白质组学方法，我们有证据表明，这种温度调节发生。此外，C.空肠温度调节可能增加在37 ℃的蛋白质表达，这些蛋白质在人类疾病过程中可能是重要的，并且似乎定义了允许同时调节许多C.空肠蛋白。我们现在建议进一步研究C. jejuni的蛋白质，重点是那些在37 C诱导的蛋白质，这些蛋白质可能是C.空肠引起人类疾病。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。利用蛋白质组学和基因芯片技术对C.空肠蛋白，并检查菌株间的变异性在37 C诱导的蛋白。具体目标2。描述了C.空肠蛋白在37 ℃诱导。阐明特异性37 C诱导蛋白在体外人上皮细胞结合和侵袭中以及在小鼠模型中定植中的作用。

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.