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

Abstract

Many of the world's warm-blooded species are chronically infected with <i>Toxoplasma gondii</i> 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 <i>T. gondii</i> and related coccidian parasites that impact human and animal health. Herein, we show that genetic ablation of <i>TgATG9</i> substantially reduces canonical autophagy and compromises bradyzoite viability. Transmission electron microscopy revealed numerous structural abnormalities occurring in ∆<i>atg9</i> bradyzoites. Intriguingly, abnormal mitochondrial networks were observed in TgATG9-deficient bradyzoites, some of which contained numerous different cytoplasmic components and organelles. ∆<i>atg9</i> 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.