Toxoplasma gondii: cyst wall

弓形虫：囊壁

• 批准号: 9132489
• 负责人: Louis M. Weiss
• 金额: $ 2.41万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-11-15 至 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9132489
• 关键词: Acetylgalactosamine; Acetylglucosamine; Acquired Immunodeficiency Syndrome; Animals; Antibodies; Apicomplexa; Appearance; Binding; Biochemical Genetics; Biogenesis; Biology; Birds; Brain; Capital; Categories; Cell Nucleus; Cells; Chorioretinitis; Chronic; Cyst; Cytoplasmic Granules; Development; Developmental Biology; Disease; Dolichos; Encephalitis; Enzymes; Equilibrium; Europe; Eye; Food; Genes; Genome; Genotype; Glycoproteins; Goals; HIV Infections; Human; Immune; Immune system; Immunologics; Infection; Investigation; Laboratories; Lead; Lectin; Lethal Dose 50; Letters; Life; Mammals; Mediating; Membrane; Methods; Mucins; Mus; Nervous system structure; Neuraxis; North America; Opportunistic Infections; Oral; Organism; Parasites; Pathogenesis; Patients; Polysaccharides; Post-Translational Protein Processing; Precipitation; Process; Proliferating; Proteins; Proteome; Proteomics; Reagent; Recurrence; Research; Research Personnel; Role; Rupture; Shapes; Signal Transduction; Single Nucleotide Polymorphism; Solid; Staging; Stress; Structure; Techniques; Therapeutic Agents; Tissues; Toxoplasma gondii; Toxoplasmosis; Transfection; United States National Institutes of Health; Vacuole; Virulent; Water; congenital infection; design; genetic approach; glycosylation; insight; latent infection; member; mutant; novel strategies; pathogen; polypeptide; prevent; rhoptry; succinylated wheat germ agglutinin; tissue culture; transmission process; vaccine development

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.

描述（由申请人提供）：Apicomplexa的成员Toxoplasma Gondii是哺乳动物的无处不在的寄生虫。这种原生动物对中枢神经系统的偏爱导致坏死性脑炎构成其在HIV感染患者中的主要表现。因为它可以通过食物或水的T. gondii传播为BNIH优先病原体类别。在初始感染期间 主持人一生的囊肿；但是，这种潜在感染的重新激活会导致脉络膜炎或脑炎等疾病。几条证据表明，曲二核分化是应力介导的，并且囊肿壁（改良的寄生虫液泡膜）包含许多阶段特异性蛋白质和糖蛋白。在本提案中，研究将集中于囊肿壁组成部分的表征。使用蛋白质组学，免疫学和遗传方法的组合，囊肿壁的组成部分将利用我们开发的技术来纯化T. gondii囊肿壁。我们已经确定了具有粘蛋白类型域的几种囊肿壁特异性蛋白。其他研究人员先前已经指出，孔糖基化发生在巨霉菌中，可能参与分化。因此，我们还将使用生化和遗传方法研究O-糖基化和粘蛋白类型链接在囊肿壁发展中的作用。总的来说，这些研究将阐明囊肿壁的组成和弓形虫的糖蛋白酶，提供试剂和见解，这些试剂和见解应证明有助于理解这种关键结构的生物学和组织。了解这种结构对于开发新策略以消除潜在感染并防止重新激活毒质量。