TOXOPLASMA BRADYZOITE CYST WALL STRUCTURE/BIOSYNTHESIS

弓形虫缓殖子包囊壁结构/生物合成

• 批准号: 6363997
• 负责人: John C Boothroyd
• 金额: $ 4.17万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6363997
• 关键词: Toxoplasma gondii; carbohydrate biosynthesis; carbohydrate structure; cell differentiation; cell wall; chitin; disease /disorder model; enzyme inhibitors; gas chromatography mass spectrometry; genetic regulation; laboratory mouse; microorganism genetics; polysaccharides; protozoal cyst; toxoplasmosis

DESCRIPTION: (Adapted from Applicant's Abstract) Toxoplasma gondii is a significant cause of disease in congenitally infected infants and patients with alterations of the immune system. The disease is perpetuated in nature by encysted forms of the parasite, either as undercooked meat infected with tissue cysts or as oocysts in food or water contaminated with cat excrement. The overall purpose of this proposal is to decipher the molecular events involved in this process, focusing on the structure and function of carbohydrate residues found in the cyst wall. The specific aims of the proposal are directed at a) elucidating structural and biosynthetic aspects of N-acetylglucosameine (GlcNAc) and N-acetylgalactosomaine (GalNAc) containing carbohydrate moieties which have been identified in cyst walls and b) relating these aspects to the biological role of these structures in differentiation of the parasite. The first aim is to determine the structure and linkage of GalNAc and GlcNAc residues in cyst glycoconjugates with the long term objective of studying their biosynthesis and ascertaining whether they serve as precursor moieties for the synthesis of the cell wall which is a key event in differentiation. The second aim is to characterize and purify chitin synthase which is developmentally regulated enzyme involved in the biosynthesis of chitin. These studies will facilitate the long term objective of delineating genetic control for differentiation at the molecular level by identifying cyst specific genes encoding developmentally regulated proteins involved in the biosynthesis of cell wall polysaccharides. The last aim is to relate the findings obtained at the structural and biochemical level to growth and differentiation of the parasite in vitro as well as in vivo in the murine model of toxoplasmosis. The ultimate goal is to design strategies to arrest differentiation, interrupt the life cycle of the parasite, and control spread of disease.

描述：（改编自申请人的摘要）弓形虫是一种 先天性感染的婴儿和患有 免疫系统的改变。这种疾病在自然界中是由 寄生虫的包囊形式，无论是未煮熟的肉感染组织 囊肿或被猫排泄物污染的食物或水中的卵囊。的 这个建议的总体目的是破译所涉及的分子事件 在这一过程中，重点关注碳水化合物的结构和功能， 残留物存在于囊壁中。该提案的具体目标是 a）阐明N-乙酰葡糖胺的结构和生物合成方面， （GlcNAc）和含碳水化合物部分的N-乙酰半乳糖胺（GalNAc） 和B）将这些方面与 这些结构在寄生虫分化中的生物学作用。的 第一个目的是确定GalNAc和GlcNAc的结构和连接 长期目标是研究它们的 生物合成和确定它们是否作为前体部分， 细胞壁的合成是分化中的关键事件。第二 目的是表征和纯化几丁质合成酶， 参与几丁质生物合成的调节酶。这些研究将 促进划定遗传控制的长期目标， 通过鉴定孢囊特异性基因在分子水平上进行区分 编码发育调节蛋白质，参与 细胞壁多糖最后一个目的是将在 在结构和生化水平上对生长分化的影响 寄生虫在体外以及在弓形虫病的小鼠模型中的体内。的 最终目标是设计策略来阻止分化，中断 寄生虫的生命周期，并控制疾病的传播。