Targeting Echinococcus multilocularis Stem ...
Type de document :
Article dans une revue scientifique
URL permanente :
Titre :
Targeting Echinococcus multilocularis Stem Cells by Inhibition of the Polo-Like Kinase EmPlk1
Auteur(s) :
Schubert, Andreas [Auteur]
Institute of Hygiene and Microbiology [Wuerzburg]
Koziol, Uriel [Auteur]
Institute of Hygiene and Microbiology [Wuerzburg]
Cailliau, Katia [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Vanderstraete, Mathieu [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dissous, Colette [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Brehm, Klaus [Auteur]
Institute of Hygiene and Microbiology [Wuerzburg]
Institute of Hygiene and Microbiology [Wuerzburg]
Koziol, Uriel [Auteur]
Institute of Hygiene and Microbiology [Wuerzburg]
Cailliau, Katia [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Vanderstraete, Mathieu [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dissous, Colette [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Brehm, Klaus [Auteur]
Institute of Hygiene and Microbiology [Wuerzburg]
Titre de la revue :
PLoS neglected tropical diseases
Numéro :
8
Pagination :
e2870
Date de publication :
2014-06-05
ISSN :
1935-2735
Mot(s)-clé(s) en anglais :
Vesicles
Xenopus oocytes
Larvae
Echinococcus
Benzimidazoles
Parasitic diseases
Stem cell therapy
Cancer treatment
Xenopus oocytes
Larvae
Echinococcus
Benzimidazoles
Parasitic diseases
Stem cell therapy
Cancer treatment
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
Background: Alveolar echinococcosis (AE) is a life-threatening disease caused by larvae of the fox-tapewormEchinococcusmultilocularis. Crucial to AE pathology is continuous infiltrative growth of the parasite’s metacestode ...
Lire la suite >Background: Alveolar echinococcosis (AE) is a life-threatening disease caused by larvae of the fox-tapewormEchinococcusmultilocularis. Crucial to AE pathology is continuous infiltrative growth of the parasite’s metacestode stage, which is drivenby a population of somatic stem cells, called germinative cells. Current anti-AE chemotherapy using benzimidazoles isineffective in eliminating the germinative cell population, thus leading to remission of parasite growth upon therapydiscontinuation. Methodology/Principal findings: We herein describe the characterization of EmPlk1, encoded by the geneemplk1, whichdisplays significant homologies to members of the Plk1 sub-family of Polo-like kinases that regulate mitosis in eukaryoticcells. We demonstrate germinative cell-specific expression ofemplk1by RT-PCR, transcriptomics, andin situhybridization.We also show that EmPlk1 can induce germinal vesicle breakdown when heterologously expressed inXenopusoocytes,indicating that it is an active kinase. This activity was significantly suppressed in presence of BI 2536, a Plk1 inhibitor that hasbeen tested in clinical trials against cancer. Addition of BI 2536 at concentrations as low as 20 nM significantly blocked theformation of metacestode vesicles from cultivatedEchinococcusgerminative cells. Furthermore, low concentrations of BI2536 eliminated the germinative cell population from mature metacestode vesiclesin vitro, yielding parasite tissue that wasno longer capable of proliferation. Conclusions/Significance: We conclude that BI 2536 effectively inactivatesE. multilocularisgerminative cells in parasitelarvaein vitroby direct inhibition of EmPlk1, thus inducing mitotic arrest and germinative cell killing. Since germinative cellsare decisive for parasite proliferation and metastasis formation within the host, BI 2536 and related compounds are verypromising compounds to complement benzimidazoles in AE chemotherapyLire moins >
Lire la suite >Background: Alveolar echinococcosis (AE) is a life-threatening disease caused by larvae of the fox-tapewormEchinococcusmultilocularis. Crucial to AE pathology is continuous infiltrative growth of the parasite’s metacestode stage, which is drivenby a population of somatic stem cells, called germinative cells. Current anti-AE chemotherapy using benzimidazoles isineffective in eliminating the germinative cell population, thus leading to remission of parasite growth upon therapydiscontinuation. Methodology/Principal findings: We herein describe the characterization of EmPlk1, encoded by the geneemplk1, whichdisplays significant homologies to members of the Plk1 sub-family of Polo-like kinases that regulate mitosis in eukaryoticcells. We demonstrate germinative cell-specific expression ofemplk1by RT-PCR, transcriptomics, andin situhybridization.We also show that EmPlk1 can induce germinal vesicle breakdown when heterologously expressed inXenopusoocytes,indicating that it is an active kinase. This activity was significantly suppressed in presence of BI 2536, a Plk1 inhibitor that hasbeen tested in clinical trials against cancer. Addition of BI 2536 at concentrations as low as 20 nM significantly blocked theformation of metacestode vesicles from cultivatedEchinococcusgerminative cells. Furthermore, low concentrations of BI2536 eliminated the germinative cell population from mature metacestode vesiclesin vitro, yielding parasite tissue that wasno longer capable of proliferation. Conclusions/Significance: We conclude that BI 2536 effectively inactivatesE. multilocularisgerminative cells in parasitelarvaein vitroby direct inhibition of EmPlk1, thus inducing mitotic arrest and germinative cell killing. Since germinative cellsare decisive for parasite proliferation and metastasis formation within the host, BI 2536 and related compounds are verypromising compounds to complement benzimidazoles in AE chemotherapyLire moins >
Langue :
Anglais
Audience :
Non spécifiée
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Collections :
Équipe(s) de recherche :
Régulation des signaux de division
Date de dépôt :
2020-02-12T15:44:32Z
2021-04-16T11:56:49Z
2021-04-16T11:56:49Z
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