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

Jin-Lei Wang (), Ting-Ting Li, Nian-Zhang Zhang, Meng Wang, Li-Xiu Sun, Zhi-Wei Zhang, Bao-Quan Fu, Hany M. Elsheikha () and Xing-Quan Zhu ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-44967-z

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