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

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 tra...

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Autores principales: Kuerbannisha Amahong, Mingzhi Yan, Jintian Li, Ning Yang, Hui Liu, Xiaojuan Bi, Dominique A. Vuitton, Renyong Lin, Guodong Lü
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:e535f1a31217449589f3fefa214108032021-11-11T10:13:11ZEgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?2235-298810.3389/fcimb.2021.747739https://doaj.org/article/e535f1a31217449589f3fefa214108032021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.747739/fullhttps://doaj.org/toc/2235-2988Cystic 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.Kuerbannisha AmahongKuerbannisha AmahongMingzhi YanMingzhi YanJintian LiJintian LiNing YangHui LiuXiaojuan BiDominique A. VuittonRenyong LinRenyong LinRenyong LinGuodong LüGuodong LüGuodong LüFrontiers Media S.A.articleEchinococcus granulosus sensu strictoglucose transporter 1WZB117cystic echinococcosisglucose uptakeMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Echinococcus granulosus sensu stricto
glucose transporter 1
WZB117
cystic echinococcosis
glucose uptake
Microbiology
QR1-502
spellingShingle Echinococcus granulosus sensu stricto
glucose transporter 1
WZB117
cystic echinococcosis
glucose uptake
Microbiology
QR1-502
Kuerbannisha Amahong
Kuerbannisha Amahong
Mingzhi Yan
Mingzhi Yan
Jintian Li
Jintian Li
Ning Yang
Hui Liu
Xiaojuan Bi
Dominique A. Vuitton
Renyong Lin
Renyong Lin
Renyong Lin
Guodong Lü
Guodong Lü
Guodong Lü
EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?
description 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.
format article
author Kuerbannisha Amahong
Kuerbannisha Amahong
Mingzhi Yan
Mingzhi Yan
Jintian Li
Jintian Li
Ning Yang
Hui Liu
Xiaojuan Bi
Dominique A. Vuitton
Renyong Lin
Renyong Lin
Renyong Lin
Guodong Lü
Guodong Lü
Guodong Lü
author_facet Kuerbannisha Amahong
Kuerbannisha Amahong
Mingzhi Yan
Mingzhi Yan
Jintian Li
Jintian Li
Ning Yang
Hui Liu
Xiaojuan Bi
Dominique A. Vuitton
Renyong Lin
Renyong Lin
Renyong Lin
Guodong Lü
Guodong Lü
Guodong Lü
author_sort Kuerbannisha Amahong
title EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?
title_short EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?
title_full EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?
title_fullStr EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?
title_full_unstemmed EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?
title_sort egglut1 is crucial for the viability of echinococcus granulosus sensu stricto metacestode: a new therapeutic target?
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/e535f1a31217449589f3fefa21410803
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