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

• Published in: Nature communications Vol. 15; no. 1; pp. 793 - 17
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 38/39; 38/44; 38/77; 38/90; 38/91; 631/326/417/2550; 631/326/417/2552; Animals; Depletion; Down-regulation; Humanities and Social Sciences; Humans; Merozoites; Merozoites - metabolism; Molecular modelling; multidisciplinary; Oocysts; Parasites; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Science; Science (multidisciplinary); Toxoplasma - metabolism; Toxoplasma gondii; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-44967-z

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. Wang et al. discovered that AP2XI-2 and AP2XII-1 negatively regulate merozoite-primed pre-sexual commitment in Toxoplasma gondii, and parasites depleted of either AP2XI-2 or AP2XII-1 can serve as a valuable in vitro model for studying merogony.