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Article Dans Une Revue International journal for parasitology. Drugs and drug resistance Année : 2024

Functional validation of novel levamisole resistance marker S168T in Haemonchus contortus

Claude L. Charvet
Cédric Neveu
Roz Laing
  • Fonction : co dernier-auteur

Résumé

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.
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hal-04574486 , version 1 (14-05-2024)

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Alistair Antonopoulos, Claude L. Charvet, Kirsty Maitland, Stephen R Doyle, Cédric Neveu, et al.. Functional validation of novel levamisole resistance marker S168T in Haemonchus contortus. International journal for parasitology. Drugs and drug resistance, 2024, 24, pp.100524. ⟨10.1016/j.ijpddr.2024.100524⟩. ⟨hal-04574486⟩
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