EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

Kuerbannisha Amahong,Renyong Lin,Ning Yang,Hui Liu,Jintian Li,Dominique A Vuitton,Guodong Lü,Mingzhi Yan,Xiaojuan Bi

doi:10.3389/fcimb.2021.747739

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, the role of GLUT1 in E. granulosus s.l. (EgGLUT1) 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 and viability by the protoscoleces of E. granulosus s.s. WZB117, a GLUT1 inhibitor, inhibited glucose uptake by E. granulosus s.s. and the viability of the metacestode in vitro. 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. 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.

Highlights

Cystic echinococcosis (CE) is a chronic and neglected zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster and listed as one of 17 neglected tropical diseases by the World Health Organization (WHO) (Larrieu et al, 2019)
Bioinformatics analysis showed that EgGLUT1-ss had one major facilitator superfamily (MFS) domain and 12 transmembrane regions, which are a typical feature of the GLUT gene (Figure 1A)
We identified EgGLUT1-ss as a crucial protein involved in glucose uptake by E. granulosus s.s. metacestode and demonstrated that functional EgGLUT1-ss was essential for energy-sourcing and survival in the intermediate host of the parasite

Summary

Introduction

Cystic echinococcosis (CE) is a chronic and neglected zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster and listed as one of 17 neglected tropical diseases by the World Health Organization (WHO) (Larrieu et al, 2019). More than 2-3 million cases are estimated worldwide (Craig et al, 2007). EgGLUT1 Is a New Drug Target costs globally committed for CE treatment are more than $3 billion per year (World Health Organization, 2019). China has a high incidence of human CE, accounting for 40% of global DALYs lost worldwide (Budke et al, 2006). Between 2012 and 2016, CE was endemic in 368 counties, with an estimated 166,098 cases of CE in China (Qian and Zhou, 2018)

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