Functional validation of novel levamisole resistance marker S168T in Haemonchus contortus
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved..
Recently, a S168T variant in the acetylcholine receptor subunit ACR-8 was associated with levamisole resistance in the parasitic helminth Haemonchus contortus. Here, we used the Xenopus laevis oocyte expression system and two-electrode voltage-clamp electrophysiology to measure the functional impact of this S168T variant on the H. contortus levamisole-sensitive acetylcholine receptor, L-AChR-1.1. Expression of the ACR-8 S168T variant significantly reduced the current amplitude elicited by levamisole compared to acetylcholine, with levamisole changing from a full to partial agonist on the recombinant L-AChR. Functional validation of the S168T mutation on modulating levamisole activity at the receptor level highlights its critical importance as both a mechanism and a marker of levamisole resistance.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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Enthalten in: |
International journal for parasitology. Drugs and drug resistance - 24(2024) vom: 12. Apr., Seite 100524 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Antonopoulos, Alistair [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 08.04.2024 Date Revised 08.04.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.ijpddr.2024.100524 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM368365182 |
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520 | |a Recently, a S168T variant in the acetylcholine receptor subunit ACR-8 was associated with levamisole resistance in the parasitic helminth Haemonchus contortus. Here, we used the Xenopus laevis oocyte expression system and two-electrode voltage-clamp electrophysiology to measure the functional impact of this S168T variant on the H. contortus levamisole-sensitive acetylcholine receptor, L-AChR-1.1. Expression of the ACR-8 S168T variant significantly reduced the current amplitude elicited by levamisole compared to acetylcholine, with levamisole changing from a full to partial agonist on the recombinant L-AChR. Functional validation of the S168T mutation on modulating levamisole activity at the receptor level highlights its critical importance as both a mechanism and a marker of levamisole resistance | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Acetylcholine receptor | |
650 | 4 | |a Functional validation | |
650 | 4 | |a Haemonchus contortus | |
650 | 4 | |a Levamisole resistance | |
650 | 4 | |a Resistance mechanism | |
650 | 4 | |a S168T | |
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650 | 7 | |a 2880D3468G |2 NLM | |
650 | 7 | |a Antinematodal Agents |2 NLM | |
650 | 7 | |a Receptors, Cholinergic |2 NLM | |
650 | 7 | |a Anthelmintics |2 NLM | |
700 | 1 | |a Charvet, Claude L |e verfasserin |4 aut | |
700 | 1 | |a Maitland, Kirsty |e verfasserin |4 aut | |
700 | 1 | |a Doyle, Stephen R |e verfasserin |4 aut | |
700 | 1 | |a Neveu, Cédric |e verfasserin |4 aut | |
700 | 1 | |a Laing, Roz |e verfasserin |4 aut | |
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