AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment

作者：Li‐Xiu Sun, Meng Wang, Tianyu Zhang, Hany M. Elsheikha, Zhiwei Zhang, Xiaonan Zheng, Bao‐Quan Fu, Xing‐Quan Zhu, Guo‐Hua Liu, Jin‐Lei Wang · 发表于：mBio · 年份：2025 · DOI：10.1128/mbio.00052-25 · 被引用次数：2 · 研究领域：Toxoplasma gondii Research Studies、Cytomegalovirus and herpesvirus research、HIV Research and Treatment

ABSTRACT Toxoplasma gondii is a widespread protozoan with a complex life cycle, characterized by transitions between various hosts and developmental stages, each tailored to a specific niche within its host. However, the regulatory mechanisms governing these life cycle transitions are not well understood. In this study, we investigated the AP2 factor AP2X-1, which is expressed during the tachyzoite and bradyzoite stages but decreases in the mature merozoite stage. Knockout of ap2X-1 significantly impaired tachyzoite invasion and replication while increasing the frequency of bradyzoite differentiation. As a component associated with the HDAC3/MORC complex, loss of ap2X-1 led to the upregulation of bradyzoite- and sexual stage-specific genes. Single-cell sequencing revealed that the ap2X-1 knockout strain exhibited a mixed population of tachyzoite-, bradyzoite-, merozoite-, and sporozoite-like parasites. Cleavage under targets and tagmentation analysis revealed a substantial overlap between AP2X-1 and the HDAC3/MORC complex at the promoters of bradyzoite- and sexual stage-specific genes. Additionally, assay for transposase-accessible chromatin with high-throughput sequencing analysis demonstrated that AP2X-1 influences chromatin compaction and accessibility, suggesting that AP2X-1 may modulate the function of the HDAC3/MORC complex to facilitate the repression of bradyzoite differentiation and sexual commitment. Loss of ap2X-1 resulted in significant attenuation of T. gondii vi...