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.
Highlights
Toxoplasma gondii, an Apicomplexan, is an obligate intracellular protozoan parasite that can cause severe human disease
Monoclonal antibody SalmonE binds to the cyst wall To identify cyst wall proteins, a hybridoma library was created from mice immunized with a lysate of T. gondii ME49 cysts purified from the brains of mice with chronic T. gondii infection
This study identifies the gene encoding the major cyst wall Dolichos biflorus Agglutinin (DBA)-binding protein CST1
Summary
Toxoplasma gondii, an Apicomplexan, is an obligate intracellular protozoan parasite that can cause severe human disease. It is estimated that a third of the human population is chronically infected with T. gondii [1], with prevalence rates ranging from a few percent to nearly 80% depending on the population [2] This parasite can cause lethal encephalitis in immune compromised individuals such as those with AIDS or organ transplant recipients on immune suppressive medications. Evidence suggests that the latent tissue cysts evade the immune response [3] and can persist for the host life span [4]. It is likely tissue cysts occasionally rupture and any released parasites [5] are cleared by immune system. Tissue cysts serve as reservoir for the reactivation of the toxoplasmosis when the host becomes immune compromised with conditions such as AIDS or organ transplantation
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