Toxoplasma gondii: cyst wall

描述(申请人提供)：弓形虫是弓形虫的一员，是哺乳动物中普遍存在的寄生虫。这种原虫倾向于中枢神经系统引起坏死性脑炎，这是艾滋病毒感染患者的主要表现。由于弓形虫可以通过食物或水传播，因此被列为NIH优先考虑的B类病原体。在初始感染期间，弓形虫快速增殖的速殖子阶段分化为缓慢复制的缓殖子阶段，这些阶段仍然潜伏在组织中。 但是，这种潜伏感染的重新激活可能会导致疾病，如绒毛膜视网膜炎或脑炎。一些证据表明，缓殖子的分化是由胁迫介导的，囊壁(一种改良的寄生虫液泡膜)含有许多阶段特有的蛋白质和糖蛋白。在本提案中，研究的重点将是囊壁成分的特征。我们将利用我们开发的弓形虫囊壁纯化技术，结合蛋白质组、免疫学和遗传学方法对囊壁的成分进行表征。我们已经鉴定了几种具有粘蛋白类型结构域的囊壁特异性蛋白。其他研究人员此前已经注意到，o-糖基化发生在弓形虫中，可能与分化有关。因此，我们还将使用生化和遗传学方法研究o-糖基化和粘蛋白类型连接在囊壁发育中的作用。总体而言，这些研究将阐明弓形虫囊壁和糖蛋白组的组成，提供有助于理解这一关键结构的生物学和组织的试剂和见解。了解这种结构对于开发消除潜伏感染和防止弓形虫病再激活的新策略很重要。 公共卫生相关性：弓形虫是一种食物和水传播的病原体，是艾滋病患者的一种机会性感染，也是先天性感染的原因之一。囊壁在这种感染的发病机制中是一个关键结构，允许传播和再激活。对这种结构形成的研究应该有助于确定控制这种致病原虫的新方法。 弓形虫是人类的一种寄生虫，它会引起感染，从而损害神经系统。这是因为它能够在宿主细胞内形成组织囊。组织囊壁对于这种生物的生存及其引起潜伏感染的能力至关重要。许多研究，包括我们实验室的研究，都表明糖蛋白参与了这一过程和囊壁的形成。这项提案将成为 囊壁及其相关糖蛋白的组成。。

DESCRIPTION (provided by applicant): Toxoplasma gondii, a member of the Apicomplexa, is a ubiquitous parasite of mammals. The predilection of this protozoan for the central nervous system causing necrotizing encephalitis constitutes its major presentation in patients with HIV infection. Because it can be transmitted by food or water T. gondii is classified as a category B NIH priority pathogen. During initial infection the rapidly proliferating tachyzoite stage of T. gondii differentiates into the slowly replicating bradyzoite stage that remain latent within tissue cysts for the life of the host; however reactivation of this latent infection can result in disease such chorioretintiis or encephalitis. Several lines of evidence suggest that bradyzoite differentiation is stress mediated and that the cyst wall (a modified parasitophorous vacuole membrane) contains many stage specific proteins and glycoproteins. In the present proposal, studies will be focused on the characterization of the components of the cyst wall. The components of the cyst wall will be characterized using a combination of proteomic, immunologic and genetic approaches taking advantage of techniques we have developed for purification of the T. gondii cyst wall. We have already identified several cyst wall specific proteins that have mucin type domains. Other investigators have previously noted that o-glycosylation occurs in T. gondii and is probably involved in differentiation. We will, therefore, also examine the role of o-glycosylation and mucin type linkages in the development of the cyst wall using biochemical and genetic approaches. Overall these studies will both elucidate the composition of the cyst wall and the glycoproteome of T. gondii providing reagents and insights that should prove useful in understanding the biology and organization of this critical structure. Understanding this structure is important for the development of new strategies to eliminate latent infection and prevent reactivation toxoplasmosis. PUBLIC HEALTH RELEVANCE: Toxoplasma gondii is a food and water borne pathogenic organism, an opportunistic infection in AIDS patients and a cause of congenital infection. The cyst wall is a key structure in the pathogenesis of this infection permitting transmission and reactivation. Investigations on the formation of this structure should help define new approaches to control of this pathogenic protozoan. Toxoplasma gondii is a parasite of humans that causes infections resulting in damage to the nervous system. This is due to its ability to form tissue cysts within host cells. The tissue cyst wall is critical for the survival of this organism and its ability to cause latent infection. Many studies, including those from our laboratory group, have suggested that glycoproteins are involved in this process and in the formation of the cyst wall. This proposal will characterize the composition of the cyst wall and its associated glycoproteins. .