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

eLife

Fengrong Wang¹  Einar B Olafsson¹  Nayanna M Mercado Soto¹  Patrick A Rimple¹  Geetha Kannan¹  Vern B Carruthers¹  David Smith¹  Tracey L Schultz¹  Manlio Di Cristina²  Isabelle Coppens³  Aude Cerutti⁴  Hoa Mai Nguyen⁴  Sébastien Besteiro⁴ 

[1] Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States;Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States;Department of Chemistry, Biology and Biotechnology, Università degli Studi di Perugia, Perugia, Italy;Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States;Laboratory of PathogenHost Interactions, UMR 5235, CNRS, Université de Montpellier, Montpellier, France;

关键词: Toxoplasma gondii;    chronic infection;    ATG9;    apicomplexa;    protozoan;    parasite;    Other;   

DOI  :  10.7554/eLife.59384

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY