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The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony

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  • Jin-Lei Wang

    (Chinese Academy of Agricultural Sciences)

  • Ting-Ting Li

    (Chinese Academy of Agricultural Sciences)

  • Nian-Zhang Zhang

    (Chinese Academy of Agricultural Sciences)

  • Meng Wang

    (Chinese Academy of Agricultural Sciences)

  • Li-Xiu Sun

    (Chinese Academy of Agricultural Sciences)

  • Zhi-Wei Zhang

    (Chinese Academy of Agricultural Sciences)

  • Bao-Quan Fu

    (Chinese Academy of Agricultural Sciences)

  • Hany M. Elsheikha

    (University of Nottingham, Sutton Bonington Campus)

  • Xing-Quan Zhu

    (Shanxi Agricultural University)

Abstract

Sexual development in Toxoplasma gondii is a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro.

Suggested Citation

  • Jin-Lei Wang & Ting-Ting Li & Nian-Zhang Zhang & Meng Wang & Li-Xiu Sun & Zhi-Wei Zhang & Bao-Quan Fu & Hany M. Elsheikha & Xing-Quan Zhu, 2024. "The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44967-z
    DOI: 10.1038/s41467-024-44967-z
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    References listed on IDEAS

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    1. Ana Vera Antunes & Martina Shahinas & Christopher Swale & Dayana C. Farhat & Chandra Ramakrishnan & Christophe Bruley & Dominique Cannella & Marie G. Robert & Charlotte Corrao & Yohann Couté & Adrian , 2024. "In vitro production of cat-restricted Toxoplasma pre-sexual stages," Nature, Nature, vol. 625(7994), pages 366-376, January.
    2. Jin-Lei Wang & Ting-Ting Li & Hany M. Elsheikha & Qin-Li Liang & Zhi-Wei Zhang & Meng Wang & L. David Sibley & Xing-Quan Zhu, 2022. "The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Abhinav Sinha & Katie R. Hughes & Katarzyna K. Modrzynska & Thomas D. Otto & Claudia Pfander & Nicholas J. Dickens & Agnieszka A. Religa & Ellen Bushell & Anne L. Graham & Rachael Cameron & Bjorn F. C, 2014. "A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium," Nature, Nature, vol. 507(7491), pages 253-257, March.
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