EgGLUT1 is Crucial for the Viability of <i>Echinococcus granulosus sensu stricto</i> Metacestode: A New Therapeutic Target?

Abstract

Background: 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 and is a valuable drug target. However, the role of GLUT1 in E. granulosus s.l. (EgGLUT1) was unknown. Methods: The EgGLUT1-ss gene was cloned from E. granulosus sensu stricto (s.s.). The function of EgGLUT1-ss was identified by interfereing with EgGLUT1-specific siRNA or GLUT1 inhibitor WZB117 in vitro. The therapeutic effect of WZB117 and its effect on the glucose metabolism of larvae of E. granulosus s.s. in vivo were further validated in murine models. Findings: Knockdown of EgGLUT1 and WZB117 inhibited the glucose uptake and the viability of the larvae of E. granulosus s.s. in vitro (P < 0.01). In addition, WZB117 showed significant 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 (P < 0.05) as efficiently as the reference drug, albendazole. Interpretation: Our results demonstrate that EgGLUT1-ss is crucial for glucose uptake by the protoscoleces of E. granulosus s.s., and its inhibitor WZB117 has a therapeutic effect on CE. Funding Information: The National Natural Science Foundation of China (82060373, 81760369 and 81360251); State Key Laboratory of Pathogenesis, Prevention and Treatment of Central Asian High Incidence Diseases Fund (SKL-HIDCA-2020-BC3); Tianshan Cedar Science and Technology Innovation Talents Support Plan of Xinjiang Uygur Autonomous Region (No. 2019XS13). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All procedures carried out with animals were approved by the Ethical Committee of the First Affiliated Hospital of Xinjiang Medical University (IACUC-20130425012).