• Login as Editor
    View Item 
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    •   Yeshiva Academic Institutional Repository
    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    The Toxoplasma gondii Cyst Wall Glycoprotein CST1 is Critical for the Structural Integrity of Brain Cysts and Their Persistence

    Thumbnail
    Date
    2014
    Author
    Tomita, Tadakimi
    Metadata
    Show full item record
    Abstract
    Toxoplasma gondii is an Apicomplexan obligate intracellular parasite that chronically infects up to one third of the human population. It is best known for causing congenital infections in immune competent hosts and opportunistic infections in immune compromised hosts. The predilection of this parasite for the central nervous system causing necrotizing encephalitis and for the eye causing chorioretinitis constitutes its major threat to patients. The development of these diseases is a consequence of the transition of bradyzoites, found within tissue cysts into actively replicating tachyzoites. Although tachyzoites and bradyzoites are well defined morphologically, little is known about how interconversion from one to the other stage occurs or what signal(s) mediate this transformation. Tachyzoites and bradyzoites are antigenically distinct. Bradyzoites are contained in a modified parasitophorous vacuole called a tissue cyst. An overriding hypothesis of this project is that the cyst wall is important in the survival of T. gondii during transmission by gastrointestinal infection and for maintaining cyst integrity during latent infection. This thesis reports my identification of and subsequent characterization of a T. gondii cyst wall glycoprotein CST1 (ToxoDB gene locus TGME49_064660). CST1 is a 250 kDa glycoprotein which contains 13 SRS domains (SAG1 related surface antigen) and a large mucin-like domain (263aa). This protein is responsible for cyst wall staining with Dolichos biflorus lectin, a commonly used marker of cyst development. Deletion of CSTI (Deltacstl) resulted in the formation of fragile brain cysts. In addition, the number of Deltacstl brain cysts formed during chronic infection was lower than that seen in wild type T. gondii suggesting that CST1 is critical for the persistence of the cysts in the central nervous system. Electron microscopy of brain cysts revealed that the cyst wall of Deltacstl parasites was much thinner and disrupted compared with the thick and organized wild type cyst wall. Analysis of the transcriptomes of wild type and mutant parasites demonstrated that disruption of CST1 dysregulated bradyzoite specific gene expression. Complementation of Deltacstl parasites with full length CST1 restored cyst sturdiness, brain cyst burden, and bradyzoite gene regulation to wild type levels. Furthermore, complementation with CST1 lacking the mucin-like domain failed to restore these Deltacstl phenotypes. T. gondii CST1 is the first cyst wall protein identified with a function of structural integrity for cyst architecture. It is a critical element in cyst wall persistence during chronic infection.
    Permanent Link(s)
    https://yulib002.mc.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3580247
    https://hdl.handle.net/20.500.12202/1462
    Collections
    • Albert Einstein College of Medicine: Doctoral Dissertations [1674]

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University
     

     

    Browse

    AllCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login as Editor

    Statistics

    View Usage Statistics

    Yeshiva University Libraries copyright © 2021  DuraSpace
    YAIR Self-Deposit | YAIR User's Guide | Take Down Policy | Contact Us
    Yeshiva University