EgGLUT1 is crucial for the viability of larvae of Echinococcus granulosus sensus lato by involving its glucose uptake
EgGLUT1 is crucial for the viability of larvae of Echinococcus granulosus sensus lato by 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.
Amahong Kuerbannisha、Liu Hui、Vuitton Dominique A.、Yang Ning、Li Jintian、Yan Mingzhi、L¨1 Guodong、Bi Xiaojuan、Lin Renyong
State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University||College of Pharmacy, Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityUniversity Bourgogne Franche-Comt¨| and French National Reference Centre for EchinococcosisState Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University||College of Pharmacy, Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University||College of Pharmacy, Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University||College of Pharmacy, Xinjiang Medical University||WHO Collaborating Centre for Prevention and Care Management of Echinococcosis, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University||WHO Collaborating Centre for Prevention and Care Management of Echinococcosis, The First Affiliated Hospital of Xinjiang Medical University||Basic Medical College, Xinjiang Medical University
基础医学药学生物科学理论、生物科学方法
cystic echinococcosisglucose transporter 1glucose uptakeWZB117
Amahong Kuerbannisha,Liu Hui,Vuitton Dominique A.,Yang Ning,Li Jintian,Yan Mingzhi,L¨1 Guodong,Bi Xiaojuan,Lin Renyong.EgGLUT1 is crucial for the viability of larvae of Echinococcus granulosus sensus lato by involving its glucose uptake[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/2021.04.02.438290.点此复制
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