title: The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence.
abstract: Toxoplasma gondii infects up to one third of the world's population. A key to the success of T. gondii as a parasite is its ability to persist for the life of its host as bradyzoites within tissue cysts. The glycosylated cyst wall is the key structural feature that facilitates persistence and oral transmission of this parasite. Because most of the antibodies and reagents that recognize the cyst wall recognize carbohydrates, identification of the components of the cyst wall has been technically challenging. We have identified CST1 (TGME49_064660) as a 250 kDa SRS (SAG1 related sequence) domain protein with a large mucin-like domain. CST1 is responsible for the Dolichos biflorus Agglutinin (DBA) lectin binding characteristic of T. gondii cysts. Deletion of CST1 results in reduced cyst number and a fragile brain cyst phenotype characterized by a thinning and disruption of the underlying region of the cyst wall. These defects are reversed by complementation of CST1. Additional complementation experiments demonstrate that the CST1-mucin domain is necessary for the formation of a normal cyst wall structure, the ability of the cyst to resist mechanical stress, and binding of DBA to the cyst wall. RNA-seq transcriptome analysis demonstrated dysregulation of bradyzoite genes within the various cst1 mutants. These results indicate that CST1 functions as a key structural component that confers essential sturdiness to the T. gondii tissue cyst critical for persistence of bradyzoite forms.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Tadakimi
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bzik
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Yan Fen
authors.initials: YF
authors.lastname: Ma
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fox
authors.affiliation: Fundamental and Computational Sciences, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Lye Meng
authors.initials: LM
authors.lastname: Markillie
authors.affiliation: Fundamental and Computational Sciences, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Taylor
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America ; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America ; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Kami
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America ; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002478:Cells, Cultured; D003560:Cysts / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D008018:Life Cycle Stages / Q000235:genetics; D010539:Permeability; D015800:Protozoan Proteins / Q000502:physiology*; D033761:Spores, Protozoan / Q000235:genetics* / Q000378:metabolism; D014122:Toxoplasma / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology / Q000469:parasitology
chemical_list: D000911:Antibodies, Monoclonal; D015800:Protozoan Proteins