Toxoplasma TgATG9 is critical for autophagy and long-term persistence in tissue cysts
- Moredun Research Institute, United Kingdom
- University of Michigan, United States
- Johns Hopkins University, United States
- Université de Montpellier, France
- Università degli Studi di Perugia, Italy
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Manlio Di Cristina
Sébastien Besteiro
Funding
National Institutes of Health (R01AI120627)
- Vern B Carruthers
National Institutes of Health (R01AI060767)
- Isabelle Coppens
Agence Nationale de la Recherche (ANR-19-CE15-0023)
- Sébastien Besteiro
Fondation pour la Recherche Médicale (FRM EQ20170336725)
- Sébastien Besteiro
National Institutes of Health (R25GM086262)
- Nayanna M Mercado Soto
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sebastian Lourido, Whitehead Institute for Biomedical Research, United States
Ethics
Animal experimentation: All laboratory animal work in this study was carried out in accordance with policies and guidelines specified by the Office of Laboratory Animal Welfare, the US Department of Agriculture, and the American Association for Accreditation of Laboratory Animal Care (AAALAC). The University of Michigan Committee on the Use and Care of Animals (IACUC) approved the animal protocol used for this study (Animal Welfare Assurance A3114-01, protocol PRO00008638).
Version history
- Received: June 1, 2020
- Accepted: April 27, 2021
- Accepted Manuscript published: April 27, 2021 (version 1)
- Version of Record published: May 17, 2021 (version 2)
Copyright
© 2021, Smith et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Toxoplasma TgATG9 is critical for autophagy and long-term persistence in tissue cysts
eLife 10:e59384.
https://doi.org/10.7554/eLife.59384
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