Nucleus-targeted effector EnP1 promotes microsporidia proliferation by obstructing H2B monoubiquitination and preventing host ferroptosis

ABSTRACT: Microsporidia, significant intracellular eukaryotic pathogens, pose a substantial threat to immunocompromised individuals. Their manipulation of host cells during infection remains poorly understood. Here, we identified EnP1, a previously reported spore wall protein, as a nucleus-targeted effector of microsporidia by a proximity biotinylation-based approach. EnP1's translocation to the host nucleus is meditated by nuclear localization signals (NLSs), where it interacts with host histone H2B upon infection. This interaction disrupts H2B monoubiquitination, 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 microsporidia infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms behind microsporidia's secretion of nuclear effectors and their control over host cell ferroptosis, ensuring their survival within the host.

ORGANISM(S): Homo sapiens

PROVIDER: GSE247835 | GEO | 2023/11/21

REPOSITORIES: GEO