EgGLUT1 is crucial for the viability of larvae ofEchinococcus granulosus sensus latoby involving its glucose uptake

ABSTRACT Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus granulosus sensu lato ( s.l. ) cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, presence and role of GLUT1 in E. granulosus s.l. (EgGLTU1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) from E. granulosus sensu stricto ( s.s. ) and found EgGLUT1-ss was crucial for glucose uptake of the protoscoleces of E. granulosus s.s.. WZB117, a GLUT1 inhibitor, inhibited glucose uptake of E. granulosus s.s. and the viability of the metacestode in vitro. In addition, WZB117 showed potent therapeutic activity in E. granulosus s.s.- infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts as well as the reference drug, albendazole. Our data have defined EgGLUT1 as a key E. granulosus s.l. vulnerability target, involved in its glucose uptake from the host; this opens a new avenue to identify drugs with an ideal activity profile for the treatment of CE.