PDF(Pubmed)
Abstract：
Microsporidia are intracellular eukaryotic pathogens that pose a substantial threat to immunocompromised hosts. The way these pathogens manipulate host cells during infection remains poorly understood. Using a proximity biotinylation strategy we established that microsporidian EnP1 is a nucleus-targeted effector that modifies the host cell environment. EnP1\'s translocation to the host nucleus is meditated by nuclear localization signals (NLSs). In the nucleus, EnP1 interacts with host histone H2B. This interaction disrupts H2B monoubiquitination (H2Bub), subsequently impacting p53 expression. Crucially, this inhibition of p53 weakens its control over the downstream target gene SLC7A11, enhancing the host cell\'s resilience against ferroptosis during microsporidian infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms by which microsporidia modify their host cells to facilitate their survival.
摘要：
微孢子虫是细胞内真核病原体，对免疫受损的宿主构成重大威胁。这些病原体在感染期间操纵宿主细胞的方式仍然知之甚少。使用邻近生物素化策略，我们确定微孢子虫EnP1是修饰宿主细胞环境的核靶向效应物。EnP1向宿主细胞核的易位通过核定位信号(NLS)进行冥想。在细胞核中，EnP1与宿主组蛋白H2B相互作用。这种相互作用破坏了H2B单氮化(H2Bub)，随后影响p53表达。至关重要的是，这种对p53的抑制作用减弱了其对下游靶基因SLC7A11的控制，增强了宿主细胞在微孢子虫感染期间抵抗铁凋亡的能力。这种有利条件促进了宿主细胞内微孢子虫的增殖。这些发现揭示了微孢子虫修饰其宿主细胞以促进其存活的分子机制。
