AP2XII-1 is a negative regulator of merogony and presexual commitment in Toxoplasma gondii

文献类型： 外文期刊

第一作者： Fan, Fuqiang

作者： Fan, Fuqiang;Xue, Lilan;Yin, Xiaoyan;Gupta, Nishith;Shen, Bang;Gupta, Nishith;Gupta, Nishith;Shen, Bang;Shen, Bang;Shen, Bang

作者机构：

关键词： AP2 transcription factors; merozoite; sexual development; MORC; merogony

期刊名称：MBIO （ 影响因子：6.4； 五年影响因子：6.9 ）

ISSN： 2150-7511

年卷期： 2023 年

页码：

收录情况： SCI

摘要： A transition from the asexual to sexual development in the widespread intracellular pathogen Toxoplasma gondii requires stage switching in its feline (definitive) host, but the mechanisms governing this process remain elusive. Here, we demonstrate a novel apicomplexan-specific transcription factor, TgAP2XII-1, that controls the transition of the acutely infectious tachyzoite stage to a presexual merozoite stage. The AP2XII-1 deletion mutants are elongated and replicate as merozoites by endopolygeny instead of endodyogeny, by which tachyzoites proliferate. Besides, the parasites lacking AP2XII-1 show a merozoite-type transcriptional profile. Indeed, AP2XII-1 directly targets many stage-specific genes via its interaction with the MORC complex, eventually repressing a repertoire of sex-related transcripts in tachyzoites. In conclusion, our work identifies AP2XII-1 as a merogony repressor, provides insight into the sexual commitment of T. gondii, and opens a gateway to culture the presexual stages of a model parasitic protist. IMPORTANCE Sexual development is vital for the transmission, genetic hybridization, and population evolution of apicomplexan pathogens, which include several clinically relevant parasites, such as Plasmodium, Eimeria, and Toxoplasma gondii. Previous studies have demonstrated different morphological characteristics and division patterns between asexual and sexual stages of the parasites. However, the primary regulation is poorly understood. A transition from the asexual to the sexual stage is supposedly triggered/accompanied by rewiring of gene expression and controlled by transcription factors and chromatin modulators. Herein, we discovered a tachyzoite-tachyzoitespecific transcriptional factor AP2XII-1, which represses the presexual development in the asexual tachyzoite stage of T. gondii. Conditional knockdown of AP2XII-1 perturbs tachyzoite proliferation by endodyogeny and drives a transition to a morphologically and transcriptionally distinct merozoite stage. The results also suggest a hierarchical transcriptional regulation of sexual development by AP2 factors and provide a path to culturing merozoites and controlling inter-host transmission of T. gondii.

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