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

Smith, David (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

Kannan, Geetha (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

Coppens, Isabelle (author): Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States

Wang, Fengrong (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

Nguyen, Hoa Mai (author): Laboratory of PathogenHost Interactions, UMR 5235, CNRS, Université de Montpellier, Montpellier, France

Cerutti, Aude (author): Laboratory of PathogenHost Interactions, UMR 5235, CNRS, Université de Montpellier, Montpellier, France

Olafsson, Einar B (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

Rimple, Patrick A (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

Schultz, Tracey L (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

Mercado Soto, Nayanna M (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

Di Cristina, Manlio (author): 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

Besteiro, Sébastien (author): Laboratory of PathogenHost Interactions, UMR 5235, CNRS, Université de Montpellier, Montpellier, France

Carruthers, Vern B (author): Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States

(creator_code:org_t)

Related links:: https://doi.org/10.7...; show more...; https://urn.kb.se/re...; https://doi.org/10.7...; show less...

Abstract Subject headings

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.

By the author/editor: Smith, David; Kannan, Geetha; Coppens, Isabell ...; Wang, Fengrong; Nguyen, Hoa Mai; Cerutti, Aude; show more...; Olafsson, Einar ...; Rimple, Patrick ...; Schultz, Tracey ...; Mercado Soto, Na ...; Di Cristina, Man ...; Besteiro, Sébast ...; Carruthers, Vern ...; show less...

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