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

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

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.

Citation

Wang, J., Li, T., Zhang, N., Wang, M., Sun, L., Zhang, Z., …Zhu, X. (2024). The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony. Nature Communications, 15(1), Article 793. https://doi.org/10.1038/s41467-024-44967-z

• Journal Article Type: Article
• Acceptance Date: Jan 10, 2024
• Online Publication Date: Jan 26, 2024
• Publication Date: Jan 26, 2024
• Deposit Date: Jan 26, 2024
• Publicly Available Date: Jan 30, 2024
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Article Number: 793
• DOI: https://doi.org/10.1038/s41467-024-44967-z
• Keywords: Parasite genetics; Parasite physiology
• Public URL: https://nottingham-repository.worktribe.com/output/30151136
• Publisher URL: https://www.nature.com/articles/s41467-024-44967-z
• Additional Information: Received: 8 July 2023; Accepted: 10 January 2024; First Online: 26 January 2024; : The authors declare no competing interests.