A novel activation-related gene P158 is essential for evagination and early development of Echinococcus multilocularis protoscoleces

BACKGROUND: Alveolar echinococcosis is a lethal zoonotic parasitic disease caused by Echinococcus multilocularis. The activation and subsequent evagination of protoscoleces (PSCs) in the host digestive tract are critical steps for establishing infection in definitive hosts, yet the underlying molecular mechanisms remain poorly understood. METHODS: In this study, we employed an in vitro PSC activation model combined with transcriptomic analysis to identify activation-associated genes. A novel gene, designated P158, was further characterized by transcriptional unit analysis and functional knockdown assays to assess its role in PSC evagination, viability, tegument integrity, energy metabolism, and early metacestode development. RESULTS: We confirmed that P158 constitutes an independent transcriptional unit from the adjacent DDX1 gene of E. multilocularis and found that P158 expression was significantly upregulated following activation. Knockdown of P158 led to a significant reduction in PSC evagination rate and impaired metacestode vesicular development in vitro. Concurrently, decreased cellular viability and damage to the microtriches indicated compromised tegument structural integrity. Further mechanistic analysis showed that P158 knockdown triggered metabolic dysregulation, characterized by reduced ATP levels, shrinkage of glycogen storage cells, and depletion of intracellular glycogen reserves. CONCLUSIONS: These findings demonstrate that P158 plays an essential role in promoting PSC evagination and early development by maintaining tegument structural integrity and regulating energy metabolism homeostasis. This study highlights P158 as a potential target for interventions aimed at blocking parasite development at the definitive host stage.