Toxoplasma TgATG9 is critical for autophagy and long-term persistence in tissue cysts

Many of the world's warm-blooded species are chronically infected with Toxoplasma gondii tissue cysts, including an estimated one-third of the global human population. The cellular processes that permit long-term persistence within the cyst are largely unknown for T. gondii and related coccidian parasites that impact human and animal health. Herein, we show that genetic ablation of TgATG9 substantially reduces canonical autophagy and compromises bradyzoite viability. Transmission electron microscopy revealed numerous structural abnormalities occurring in Datg9 bradyzoites. Intriguingly, abnormal mitochondrial networks were observed in TgATG9-deficient bradyzoites, some of which contained numerous different cytoplasmic components and organelles. Datg9 bradyzoite fitness was drastically compromised in vitro and in mice, with very few brain cysts identified in mice 5 weeks post-infection. Taken together, our data suggests that TgATG9, and by extension autophagy, is critical for cellular homeostasis in bradyzoites and is necessary for long-term persistence within the cyst of this coccidian parasite.

Automated summary

This study indicates that genetic ablation of TgATG9 substantially reduces canonical autophagy and compromises the viability of T. gondii bradyzoites. Abnormal mitochondrial networks were observed in TgATG9-deficient bradyzoites, which led to compromised fitness both in vitro and in mice. Overall, TgATG9, and autophagy as a whole, play a critical role in maintaining cellular homeostasis in bradyzoites and are necessary for long-term persistence within the cyst of this coccidian parasite.