The secretory effector Sce1 licenses fungal virulence by masking the immunogenic β-1,3-glucan and promoting apoptosis of the host cells.

deploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence. However, the intricate interactions between the fungus and the host remain poorly understood, and a comprehensive inventory of fungal virulence factors has yet to be established. In this study, we identified a secretory effector protein Sce1, whose induction and secretion are associated with vagina-simulative conditions and chlamydospore formation. Sequence alignment showed that Sce1 belongs to a Pir family in , which is conserved across several fungi and primarily characterized as a β-glucan binding protein in the . Mechanically, Sce1 is primarily localized to the cell wall in a cleaved form as an alkali-labile β-1,3-glucan binding protein and plays a role in masking β-glucan in acidic environments and chlamydospores, a feature that might underline ' ability to evade host immunity. Further, a cleaved short form of Sce1 protein could be released into extracellular compartments and presented in bone marrow-derived macrophages infected with chlamydospores. This cleaved short form of Sce1 also demonstrated a unique ability to trigger the caspases-8/9-dependent apoptosis in various host cells. Correspondingly, genetic deletion of led to dampened vaginal colonization of and diminished fungal virulence during systemic infection. The discovery of Sce1 as a versatile virulence effector that executes at various compartments sheds light on the fungus-host interactions and pathogenesis.