Inhibition of EgRad50 leads to impaired DNA repair in Echinococcus granulosus sensu stricto

The parasitic disease known as cystic echinococcosis (CE) is a significant zoonotic condition caused by Echinococcus granulosus sensu lato (s.l.). The current lack of safe and effective pharmacological treatments necessitates urgent efforts to identify and develop novel drug targets and therapeutic molecules. This study investigates the role of DNA repair protein 50 (Rad50) in Echinococcus granulosus sensu stricto (s.s.) and evaluates whether it serve as a viable target for CE. Three small interfering RNA (siRNA) fragments targeting EgRad50 were introduced into E. granulosus s.s. via electroporation, and qRT-PCR, Western blot, and immunofluorescence were performed to assess EgRad50 localization and expression. The survival rate of E. granulosus s.s. was evaluated through in vitro culture, DNA damage was assessed using a comet assay, and the impact of EgRad50 knockdown on DNA repair and ferroptosis was analyzed via Western blot. EgRad50 is expressed during the protoscolece (PSC) and metacestode (MTC) stages of E. granulosus s.s. and the knockdown of EgRad50 reduced the viability of E. granulosus s.s. PSCs in vitro. Moreover, inhibition of EgRad50 downregulates ATR phosphorylation levels and further activates ferroptosis, leading to the death of E. granulosus s.s. This investigation sheds light on the preliminary role of EgRad50 in DNA repair, highlighting its importance for parasite survival and suggesting it as a new potential drug target for CE therapy. The selective targeting of EgRad50 may facilitate a more effective resolution to the clinical challenges presented by CE.