Type III secretion antigen delivery system assembled in non-replicating platform

非复制平台组装的III型分泌抗原递送系统

• 批准号: 7670754
• 负责人: Jorge E Galan
• 金额: $ 23.6万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670754
• 关键词: Antigens; Bacteria; Base Sequence; Campylobacter jejuni; Cell Line; Cells; Cellular biology; Complication; Development; Diarrhea; Disease; Epithelial Cells; Event; Food Supply; Genome; Goals; Growth; Guillain-Barré Syndrome; In Vitro; Infection; Inflammatory; Intestines; Lead; Mammalian Cell; Mediating; Metabolic; Molecular; Pathogenicity; Pathology; Patients; Production; Research Project Grants; System; Therapeutic; United States; animal tissue; base; biodefense; cytokine; foodborne; intestinal epithelium; tissue culture; uptake

Campylobacter jejuni is the most common cause of food-born diarrhea in the United States. Although it is most often associated with self-limiting diarrheal disease, a small proportion of infected patients develop a more serious neuro-degenerative complication known as Guillain-Barre Syndrome. Despite the availability of the entire nucleotide sequence of the C. jejuni genome, remarkably little is known about its mechanisms of pathogenicity. The pathology associated with C. jejuni infections, combined with a variety of observations in experimental animals and tissue culture systems, suggest that disease may be the result of the development of an intimate functional interface between these bacteria and intestinal epithelial cells. As a consequence of these intimate interactions, C. jejuni can gain access to the cells that line the intestinal epithelium and can stimulate the production of pro-inflammatory cytokines. The molecular and cellular bases for these events are poorly understood. The long term goal of this research project is to gain a better understanding of the molecular and cell biology of the interactions of C. jejuni with host cells. We propose to execute the following specific aims: 1) To identify C. jejuni determinants which mediate its interactions with host cells; 2) To deepen the understanding of the cell biology of critical events leading to C. jejuni uptake into and survival within intestinal epithelial cells; 3) To investigate the C. jejuni metabolic reprogramming that allows its survival within host cells; and 4) To define the proteoglycome of C. jejuni after growth in vitro or within mammalian cells.

空肠弯曲菌是美国最常见的食源性腹泻原因。虽然 大多数情况下与自限性淋病有关，一小部分感染患者会发展为 更严重的神经退行性并发症称为格林-巴利综合征。尽管有 C.空肠基因组，非常少的是知道它的机制， 致病性与C.空肠感染，结合各种观察结果， 实验动物和组织培养系统，表明疾病可能是发展的结果， 在这些细菌和肠上皮细胞之间有一个密切的功能界面。的结果 这些亲密的互动，C。空肠可以接近肠上皮细胞， 刺激促炎细胞因子的产生。这些事件的分子和细胞基础 我们对此知之甚少。本研究项目的长期目标是更好地了解 分子和细胞生物学的相互作用的C。空肠与宿主细胞。我们建议执行以下措施 具体目标：1）识别C.介导其与宿主细胞相互作用的空肠决定簇; 2） 加深对导致C的关键事件的细胞生物学的理解。空肠摄取和存活 肠上皮细胞内的C.空肠代谢重编程， 在宿主细胞内的存活; 4）确定C.空肠在体外或体内生长后 哺乳动物细胞