Details

Autor(en) / Beteiligte

• Sokol-Borrelli, Sarah L.
• Reilly, Sarah M.
• Holmes, Michael J.
• Orchanian, Stephanie B.
• Massmann, Mackenzie D.
• Sharp, Katherine G.
• Cabo, Leah F.
• Alrubaye, Hisham S.
• Martorelli Di Genova, Bruno
• Lodoen, Melissa B.
• Sullivan, William J.
• Boyle, Jon P.

Titel

A transcriptional network required for bradyzoite development in Toxoplasma gondii is dispensable for recrudescent disease

Ist Teil von

• Nature communications, 2023-09, Vol.14 (1), p.6078-20, Article 6078

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Identification of regulators of Toxoplasma gondii bradyzoite development and cyst formation is the most direct way to address the importance of parasite development in long-term persistence and reactivation of this parasite. Here we show that a T. gondii gene (named Regulator of Cystogenesis 1 ; ROCY1 ) is sufficient for T. gondii bradyzoite formation in vitro and in vivo. ROCY1 encodes an RNA binding protein that has a preference for 3’ regulatory regions of hundreds of T. gondii transcripts, and its RNA-binding domains are required to mediate bradyzoite development. Female mice infected with Δ ROCY1 parasites have reduced (>90%) cyst burden. While viable parasites can be cultivated from brain tissue for up to 6 months post-infection, chronic brain-resident Δ ROCY1 parasites have reduced oral infectivity compared to wild type. Despite clear defects in bradyzoite formation and oral infectivity, Δ ROCY1 parasites were able to reactivate with similar timing and magnitude as wild type parasites for up to 5 months post-infection. Therefore while ROCY1 is a critical regulator of the bradyzoite developmental pathway, it is not required for parasite reactivation, raising new questions about the persisting life stage responsible for causing recrudescent disease. Toxoplasma gondii can develop into dormant bradyzoites that persist in tissue and can be reactivated. Here the authors identify an RNA binding protein that they call Regulator of Cystogenesis 1 (ROCY1), and show that it is required for bradyzoite development in vitro and in vivo but is not required for long term persistence of parasites that reactivate in a mouse model of recrudescence.