Microsporidia is an opportunistic pathogenic fungus that infects a wide range of hosts and has a unique invasion mechanism.The purpose of this study was to investigate whether microsporidia secrete effectors into the host nucleus and how they interact with the host to create a permissive environment for successful parasitic association.To explore this,the biotin proximity labeling was utilized to selectively biotinylate whole host nucleus.And the Endospore protein 1(EnP1) was identified as one of the nucleus-targeted effectors of microsporidia using mass spectrometry.Overexpression of EnP1 could increase the proliferation of microsporidia in the host cells,and this promoting impact could be minimized when the nuclear localization signals(NLS) sequence of EnP1 was truncated.Further investigation revealed that EnP1interact with the core nucleosome protein histone 2B(H2B).Notably,the mono-ubiquitination level of H2B(H2Bub1) was significantly decreased by EnP1 overexpression.These findings indicated that EnP1 could increase the susceptibility of host cells to microsporidia infection by being translocated to the host nucleus and interacting with H2B.Additionally,transcriptome sequencing analysis and immunoblot assay demonstrated that EnP1 mitigated ferroptosis by downregulating TP53 and upregulating SLC7A11.The ability of E.hellem to prevent host cell ferroptosis was positively associated with thDibutyryl-cAMP研究购买e protein expression level of EnP1.Furthermore,increasing the H2Bub1 through overexpression of the specific ubiquitin ligase RNF20 enhanced the TP53 expression and reduced pathogen proliferation in vitro,while decreasing H2Bub1 had the opposite effect.These findings unveiled that EnP1 decrease the H2Bub1,resulting in reduced TP53 expression.Consequently,this leads to increased expression of SLC7A11,inhibiting host ferroptosis and ultimately promoting microsporidia proliferation.Overall,this study provides compelling evidence that the effectinundative biological controlor protein EnP1,secrete更多d by microsporidia,plays a crucial role in manipulating host cell responses and establishing a successful parasitic association.Understanding the mechanisms underlying this interaction may contribute to the development of targeted interventions against microsporidia infections.