Elucidating the Role of the Essential Kinase TgGSK in the Human Parasite Toxoplasma Gondii

Abstract

Toxoplasma gondii is an intracellular parasite that infects nearly a third of the world’s human population. While infection is largely asymptomatic in an immunocompetent host, Toxoplasma infection in immunocompromised or immunosuppressed individuals can lead to toxoplasmosis, which can include brain lesions and lead to death. Similarly, toxoplasmosis can result in birth defects, brain swelling, and blindness of a developing fetus in the case of a congenital infection. With minimal treatments for toxoplasmosis available, it is crucial to study parasite-specific processes that could be potential drug targets for the treatment of toxoplasmosis. Toxoplasma gondii divides through a unique process known as endodyogeny, where two daughter parasites are formed within a mother. In this study, we investigated a novel protein called TgGSK that is crucial for proper parasite division. Experiments reveal that TgGSK changes its localization within the parasite dependent on the stage of division. Knockdown of TgGSK causes abnormal division phenotypes and causes Toxoplasma to be unable to complete its propagation cycle. We determined through microscopy and phosphoproteomics that TgGSK may play its role in parasite division through an interaction with the centrosome, an organelle which is a main feature of cell division in many organisms. Our findings suggest that TgGSK also regulates messenger RNA processing. Finally, our study suggests that TgGSK is regulated and stabilized through acetylation from the GCN5b lysine acetyltransferase complex. Taken together, we have performed an in-depth study of the functional role of the essential protein TgGSK in Toxoplasma gondii. This and future studies have potential to demonstrate that TgGSK is a parasite-specific drug target for the therapeutic treatment of toxoplasmosis.