Toxoplasma gondii: cyst wall

弓形虫：囊壁

• 批准号: 8579872
• 负责人: Louis M. Weiss
• 金额: $ 41.75万
• 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 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8579872
• 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; Genetic; 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; 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（Apicomplexa）的一种成员，是哺乳动物中普遍存在的寄生虫。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传播。弓形虫被归类为NIH优先的B类病原体。在感染初期，T.弓形虫分化为缓慢复制的缓殖子阶段， 囊肿的宿主的生命;然而，这种潜伏感染的重新激活可导致疾病，如脉络膜视网膜炎或脑炎。一些证据表明，缓殖子分化是压力介导的，囊壁（一个修改的寄生虫液泡膜）包含许多阶段特异性蛋白质和糖蛋白。在本提案中，研究将集中在囊壁成分的表征上。利用我们开发的T.弓形虫囊壁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。其他研究者先前已经注意到O-糖基化发生在T。gondii并可能参与分化。因此，我们也将研究的作用，o-糖基化和粘蛋白类型的联系，在发展中的囊壁使用生化和遗传学的方法。总之，这些研究将阐明T.弓形虫提供的试剂和见解，应证明有助于了解生物学和组织的这一关键结构。了解这种结构对于开发新的策略以消除潜伏感染和预防再激活弓形虫病是重要的。