In vitro production of cat-restricted Toxoplasma pre-sexual stages

Antunes, Ana Vera and Shahinas, Martina and Swale, Christopher and Farhat, Dayana C. and Ramakrishnan, Chandra and Bruley, Christophe and Cannella, Dominique and Robert, Marie G. and Corrao, Charlotte and Couté, Yohann and Hehl, Adrian B. and Bougdour, Alexandre and Coppens, Isabelle and Hakimi, Mohamed-Ali (2023) In vitro production of cat-restricted Toxoplasma pre-sexual stages. Nature. ISSN 0028-0836

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Abstract

Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described1,2. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. 1), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission.

Item Type: Article
Subjects: Archive Paper Guardians > Geological Science
Depositing User: Unnamed user with email support@archive.paperguardians.com
Date Deposited: 14 Dec 2023 10:49
Last Modified: 14 Dec 2023 10:49
URI: http://archives.articleproms.com/id/eprint/2531

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