The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony
Jin-Lei Wang1, Ting-Ting Li2, Nian-Zhang Zhang2
1State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, People's Republic of China. hany.elsheikha@nottingham.ac.uk.
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.
Insights
Two transcription factors, AP2XI-2 and AP2XII-1, were found to suppress sexual commitment in Toxoplasma gondii. Their depletion triggers asexual reproduction (merogony) under specific conditions, offering new research models.
Area of Science:
- Parasitology
- Molecular Biology
- Cell Biology
Background:
- Sexual development in *Toxoplasma gondii* leads to oocyst production, a key factor in human infections.
- The molecular control of sexual commitment in *Toxoplasma gondii* is not well understood.
Purpose of the Study:
- To investigate the molecular mechanisms regulating sexual commitment in *Toxoplasma gondii*.
- To identify key regulators involved in suppressing pre-sexual commitment during asexual development.
Main Methods:
- Investigated the roles of transcription factors AP2XI-2 and AP2XII-1 in *Toxoplasma gondii* sexual development.
- Utilized gene depletion strategies in the type II Pru strain under varying pH conditions (neutral and alkaline).
- Identified AP2XI-2-interacting proteins involved in regulating merozoite programming.
Main Results:
- AP2XI-2 and AP2XII-1 function as negative regulators of sexual commitment.
- Depletion of AP2XI-2 induced merogony and merozoite production in alkaline, but not neutral, media.
- AP2XII-1 depletion promoted merogony in neutral and alkaline conditions, with greater effects in alkaline media.
- Two additional proteins interacting with AP2XI-2 were identified as repressors of merozoite development.
Conclusions:
- A network of factors, including AP2XI-2 and AP2XII-1, intricately regulates pre-sexual commitment in *Toxoplasma gondii*.
- AP2XI-2 or AP2XII-1-depleted *Toxoplasma gondii* Pru strains provide valuable models for in vitro merogony studies.
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