Toxoplasma gondii: cyst wall

弓形虫：囊壁

• 批准号: 8766544
• 负责人: Louis M. Weiss
• 金额: $ 39.34万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8766544
• 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）：弓形虫是顶复门的成员，是哺乳动物中普遍存在的寄生虫。这种原虫对中枢神经系统的偏好导致坏死性脑炎，这是其在 HIV 感染患者中的主要表现。由于它可以通过食物或水传播，弓形虫被列为 NIH B 类优先病原体。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，该阶段仍潜伏在组织内 包囊伴随宿主一生；然而，这种潜伏感染的重新激活可能导致脉络膜视网膜炎或脑炎等疾病。多项证据表明，缓殖子分化是应激介导的，并且囊壁（改良的寄生液泡膜）含有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成分的表征。将利用我们开发的纯化弓形虫囊壁的技术，结合蛋白质组学、免疫学和遗传学方法来表征囊壁的成分。我们已经鉴定了几种具有粘蛋白型结构域的囊壁特异性蛋白质。其他研究人员此前曾指出，弓形虫中存在 O-糖基化，并且可能参与分化。因此，我们还将使用生化和遗传学方法研究o-糖基化和粘蛋白型连接在囊壁发育中的作用。总的来说，这些研究将阐明弓形虫包囊壁和糖蛋白组的组成，提供试剂和见解，有助于理解这一关键结构的生物学和组织。了解这种结构对于制定消除潜伏感染和防止弓形虫病重新激活的新策略非常重要。