TY - JOUR TI - Toxoplasma TgATG9 is critical for autophagy and long-term persistence in tissue cysts AU - Smith, David AU - Kannan, Geetha AU - Coppens, Isabelle AU - Wang, Fengrong AU - Nguyen, Hoa Mai AU - Cerutti, Aude AU - Olafsson, Einar B AU - Rimple, Patrick A AU - Schultz, Tracey L AU - Mercado Soto, Nayanna M AU - Di Cristina, Manlio AU - Besteiro, Sébastien AU - Carruthers, Vern B A2 - Lourido, Sebastian A2 - Soldati-Favre, Dominique VL - 10 PY - 2021 DA - 2021/04/27 SP - e59384 C1 - eLife 2021;10:e59384 DO - 10.7554/eLife.59384 UR - https://doi.org/10.7554/eLife.59384 AB - 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 ∆atg9 bradyzoites. Intriguingly, abnormal mitochondrial networks were observed in TgATG9-deficient bradyzoites, some of which contained numerous different cytoplasmic components and organelles. ∆atg9 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. KW - Toxoplasma gondii KW - chronic infection KW - ATG9 KW - apicomplexa KW - protozoan KW - parasite JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -