Campylobacter jejuni proteins induced at 37C

描述(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，已被美国国立卫生研究院列为食源性B类生物恐怖分子。除了严重胃肠炎(在美国每年240万例)造成的巨大疾病负担外，空肠弯曲菌感染与格林-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瘫痪，可能是由针对空肠弯曲菌抗原的自身免疫抗体引起的。家禽群中普遍存在无症状的空肠弯曲菌，最可能的传播途径可能是通过食用受污染的禽肉。在其自然栖息地，空肠弯曲菌能够在两种不同的温度下茁壮成长，42C(鸡的核心温度)和37C(人类)。因此，很可能存在对空肠弯曲菌蛋白质的温度调节，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。利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了。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℃的表达，并似乎定义了允许同时调节许多空肠弯曲菌蛋白质的全球调控网络。我们现在建议进一步研究空肠弯曲菌的温度调节，重点是那些在37℃诱导的蛋白质，这些蛋白质可能是空肠弯曲菌在人类中致病所必需的。我们将通过以下三个特定目标来实现这些目标：特定目标1.利用蛋白质组学和微阵列技术，鉴定和定位在37℃诱导的空肠弯曲菌蛋白，并检测37℃诱导蛋白的菌株间变异性。特定目的2.鉴定在37℃诱导的空肠弯曲菌蛋白的功能和调节。特定目的3.阐明特定的37 C诱导蛋白在体外与人上皮细胞结合和侵袭以及在小鼠模型中的定植作用。

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.