Oral ingestion of Toxoplasma gondii cysts establishes a chronic infection marked by the development of cysts in the central nervous system. Reactivation of dormant Toxoplasma gondii cysts in the central nervous system in AIDS patients causes Toxoplasmic encephalitis, a clinically difficult to treat and frequently lethal encephalitis. The parasite factors that enable the chronic persistence and oral infectivity of cysts are still poorly understood. We hypothesize that the ROP35 kinase and other members of the Toxoplasma gondii WNG kinase family play important roles in maintaining persisting cysts and their oral infectivity. This study will characterize the role of ROP35 in mediating successful chronic infection, and the role of WNG kinases, and their protein complexes, that enable the persistence of viable and orally infectious Toxoplasma gondii cysts.
Toxoplasma gondii chronically infects 1 to 2 billion people. Reactivation of chronic infection causes severe and often lethal encephalitis in AIDS patients. There is no available treatment for chronic infection, and there is no current approach to prevent the reactivation of chronic infection. This lack of progress is due to our poor understanding of how chronic infection develops and is maintained. In this project, we will investigate how a parasite kinase (ROP35) controls the development and maintenance of chronic infection, and how WNG kinases maintain oral infectivity of cysts. This project will elucidate how this medically important parasite manipulates the host to maintain a successful chronic infection.