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UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus

The nematode Haemonchus contortus, a gastrointestinal parasite of ruminants, can severely burden livestock production. Although anthelmintics are the mainstay in the treatment of haemonchosis, their efficacy diminishes due to drug-resistance development in H. contortus. An increased anthelmintics in...

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Autores principales: Kellerová, Pavlína, Navrátilová, Martina, Nguyen, Linh Thuy, Dimunová, Diana, Raisová Stuchlíková, Lucie, Štěrbová, Karolína, Skálová, Lenka, Matoušková, Petra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726322/
https://www.ncbi.nlm.nih.gov/pubmed/33324241
http://dx.doi.org/10.3389/fphys.2020.594116
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author Kellerová, Pavlína
Navrátilová, Martina
Nguyen, Linh Thuy
Dimunová, Diana
Raisová Stuchlíková, Lucie
Štěrbová, Karolína
Skálová, Lenka
Matoušková, Petra
author_facet Kellerová, Pavlína
Navrátilová, Martina
Nguyen, Linh Thuy
Dimunová, Diana
Raisová Stuchlíková, Lucie
Štěrbová, Karolína
Skálová, Lenka
Matoušková, Petra
author_sort Kellerová, Pavlína
collection PubMed
description The nematode Haemonchus contortus, a gastrointestinal parasite of ruminants, can severely burden livestock production. Although anthelmintics are the mainstay in the treatment of haemonchosis, their efficacy diminishes due to drug-resistance development in H. contortus. An increased anthelmintics inactivation via biotransformation belongs to a significant drug-resistance mechanism in H. contortus. UDP-glycosyltransferases (UGTs) participate in the metabolic inactivation of anthelmintics and other xenobiotic substrates through their conjugation with activated sugar, which drives the elimination of the xenobiotics due to enhanced solubility. The UGTs family, in terms of the biotransformation of commonly used anthelmintics, has been well described in adults as a target stage. In contrast, the free-living juvenile stages of H. contortus have attracted less attention. The expression of UGTs considerably varies throughout the life cycle of the juvenile nematodes, suggesting their different roles. Furthermore, the constitutive expression in a susceptible strain with two resistant strains shows several resistance-related changes in UGTs expression, and the exposure of juvenile stages of H. contortus to albendazole (ABZ) and ABZ-sulfoxide (ABZSO; in sublethal concentrations) leads to the increased expression of several UGTs. The anthelmintic drug ABZ and its primary metabolite ABZSO biotransformation, tested in the juvenile stages, shows significant differences between susceptible and resistant strain. Moreover, higher amounts of glycosidated metabolites of ABZ are formed in the resistant strain. Our results show similarly, as in adults, the UGTs and glycosidations significant for resistance-related differences in ABZ biotransformation and warrant further investigation in their individual functions.
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spelling pubmed-77263222020-12-14 UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus Kellerová, Pavlína Navrátilová, Martina Nguyen, Linh Thuy Dimunová, Diana Raisová Stuchlíková, Lucie Štěrbová, Karolína Skálová, Lenka Matoušková, Petra Front Physiol Physiology The nematode Haemonchus contortus, a gastrointestinal parasite of ruminants, can severely burden livestock production. Although anthelmintics are the mainstay in the treatment of haemonchosis, their efficacy diminishes due to drug-resistance development in H. contortus. An increased anthelmintics inactivation via biotransformation belongs to a significant drug-resistance mechanism in H. contortus. UDP-glycosyltransferases (UGTs) participate in the metabolic inactivation of anthelmintics and other xenobiotic substrates through their conjugation with activated sugar, which drives the elimination of the xenobiotics due to enhanced solubility. The UGTs family, in terms of the biotransformation of commonly used anthelmintics, has been well described in adults as a target stage. In contrast, the free-living juvenile stages of H. contortus have attracted less attention. The expression of UGTs considerably varies throughout the life cycle of the juvenile nematodes, suggesting their different roles. Furthermore, the constitutive expression in a susceptible strain with two resistant strains shows several resistance-related changes in UGTs expression, and the exposure of juvenile stages of H. contortus to albendazole (ABZ) and ABZ-sulfoxide (ABZSO; in sublethal concentrations) leads to the increased expression of several UGTs. The anthelmintic drug ABZ and its primary metabolite ABZSO biotransformation, tested in the juvenile stages, shows significant differences between susceptible and resistant strain. Moreover, higher amounts of glycosidated metabolites of ABZ are formed in the resistant strain. Our results show similarly, as in adults, the UGTs and glycosidations significant for resistance-related differences in ABZ biotransformation and warrant further investigation in their individual functions. Frontiers Media S.A. 2020-11-26 /pmc/articles/PMC7726322/ /pubmed/33324241 http://dx.doi.org/10.3389/fphys.2020.594116 Text en Copyright © 2020 Kellerová, Navrátilová, Nguyen, Dimunová, Raisová Stuchlíková, Štěrbová, Skálová and Matoušková. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Kellerová, Pavlína
Navrátilová, Martina
Nguyen, Linh Thuy
Dimunová, Diana
Raisová Stuchlíková, Lucie
Štěrbová, Karolína
Skálová, Lenka
Matoušková, Petra
UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
title UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
title_full UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
title_fullStr UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
title_full_unstemmed UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
title_short UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
title_sort udp-glycosyltransferases and albendazole metabolism in the juvenile stages of haemonchus contortus
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726322/
https://www.ncbi.nlm.nih.gov/pubmed/33324241
http://dx.doi.org/10.3389/fphys.2020.594116
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