Toxoplasma gondii PROP1 is critical for autophagy and parasite viability during chronic infection

Abstract

Macroautophagy is an important cellular process involving lysosomal degradation of cytoplasmic components, facilitated by autophagy-related proteins (ATGs). In the protozoan parasite Toxoplasma gondii, autophagy has been demonstrated to play a key role in adapting to stress and persistence of chronic infection. Despite limited knowledge about the core autophagy machinery in T. gondii, two PROPPIN family proteins (TgPROP1 and TgPROP2) have been identified with homology to Atg18/WIPI. Prior research in acute stage tachyzoites suggests that TgPROP2 is predominantly involved in a non-autophagic function, specifically apicoplast biogenesis, while TgPROP1 may be involved in canonical autophagy. Here, we investigated the distinct roles of TgPROP1 and TgPROP2 in chronic stage T. gondii bradyzoites, revealing a critical role for TgPROP1, but not TgPROP2, in bradyzoite autophagy. Conditional knockdown of TgPROP2 did not impair bradyzoite autophagy. In contrast, TgPROP1 KO parasites had impaired autolysosome formation, reduced cyst burdens in chronically infected mice, and decreased viability. Together, our findings clarify the indispensable role of TgPROP1 to T. gondii autophagy and chronic infection. ImportanceIt is estimated that up to a third of the human population is chronically infected with Toxoplasma gondii; however, little is known about how this parasite persists long term within its hosts. Autophagy is a self-eating pathway that has recently been shown to play a key role in parasite persistence, yet few proteins that carry out this process during T. gondii chronic infection are known. Here, we provide evidence for a non-redundant role of TgPROP1, a protein important in the early steps of the autophagy pathway. Genetic disruption of TgPROP1 resulted in impaired autophagy and chronic infection of mice. Our results reveal a critical role for TgPROP1 in autophagy and underscore the importance of this pathway in parasite persistence.