Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay

Abstract Grazing ruminants suffer from various helminth infections particularly those caused by gastrointestinal nematode (GIN) parasites, which have a considerable impact on their welfare and productivity. To treat these infections, the intensive use of macrocyclic lactone (ML) anthelmintics has le...

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Main Authors: Mélanie Alberich, Marie Garcia, Julie Petermann, Clara Blancfuney, Sophie Jouffroy, Philippe Jacquiet, Anne Lespine
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02866-3
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author Mélanie Alberich
Marie Garcia
Julie Petermann
Clara Blancfuney
Sophie Jouffroy
Philippe Jacquiet
Anne Lespine
author_facet Mélanie Alberich
Marie Garcia
Julie Petermann
Clara Blancfuney
Sophie Jouffroy
Philippe Jacquiet
Anne Lespine
author_sort Mélanie Alberich
collection DOAJ
description Abstract Grazing ruminants suffer from various helminth infections particularly those caused by gastrointestinal nematode (GIN) parasites, which have a considerable impact on their welfare and productivity. To treat these infections, the intensive use of macrocyclic lactone (ML) anthelmintics has led to the emergence of drug-resistant parasite populations worldwide. The standard method for detecting resistance, the Faecal Egg Count Reduction Test (FECRT), is susceptible to misinterpretation, leading to flawed management decisions that undermine parasite control efforts. Thus, there is a pressing need for robust resistance detection methods in field parasites. We investigated the potential of the WMicrotracker motility assay (WMA), previously unexplored in ML resistance assessment. The assay first compared ivermectin (IVM) susceptibility among wild-type Bristol N2 (N2B), IVM-selected (IVR10), and nhr-8 loss-of-function (AE501; nhr8(ok186)) Caenorhabditis elegans strains. Dose-response curves indicated that IVR10 had a 2.12-fold reduction in sensitivity to IVM compared to N2B. Additionally, cross-resistance assessment showed that IVR10 exhibited decreased sensitivity to moxidectin (MOX) and eprinomectin (EPR) relative to N2B. Further investigation conducted on Haemonchus contortus revealed significant differences in drug potency between susceptible and resistant isolates, with MOX demonstrating the highest efficacy. Resistance factors (RF) highlighted the substantial resistance of the isolate collected in a farm with EPR-treatment failure. The WMA effectively discriminated susceptible from resistant isolates in both C. elegans and H. contortus. Our findings demonstrate, for the first time, the relevance of WMA as a phenotypic assay for detecting ML resistance in nematodes by measuring their motility response. This research sheds light on a novel approach for monitoring drug resistance, vital for effective parasite management strategies.
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spelling doaj-art-a867405295ba4b35944ca22a4c2d3fe92025-08-20T03:48:18ZengNature PortfolioScientific Reports2045-23222025-05-0115111310.1038/s41598-025-02866-3Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assayMélanie Alberich0Marie Garcia1Julie Petermann2Clara Blancfuney3Sophie Jouffroy4Philippe Jacquiet5Anne Lespine6INTHERES, Université de Toulouse, INRAE, ENVTINTHERES, Université de Toulouse, INRAE, ENVTIHAP, Université de Toulouse, INRAE, ENVTINTHERES, Université de Toulouse, INRAE, ENVTIHAP, Université de Toulouse, INRAE, ENVTIHAP, Université de Toulouse, INRAE, ENVTINTHERES, Université de Toulouse, INRAE, ENVTAbstract Grazing ruminants suffer from various helminth infections particularly those caused by gastrointestinal nematode (GIN) parasites, which have a considerable impact on their welfare and productivity. To treat these infections, the intensive use of macrocyclic lactone (ML) anthelmintics has led to the emergence of drug-resistant parasite populations worldwide. The standard method for detecting resistance, the Faecal Egg Count Reduction Test (FECRT), is susceptible to misinterpretation, leading to flawed management decisions that undermine parasite control efforts. Thus, there is a pressing need for robust resistance detection methods in field parasites. We investigated the potential of the WMicrotracker motility assay (WMA), previously unexplored in ML resistance assessment. The assay first compared ivermectin (IVM) susceptibility among wild-type Bristol N2 (N2B), IVM-selected (IVR10), and nhr-8 loss-of-function (AE501; nhr8(ok186)) Caenorhabditis elegans strains. Dose-response curves indicated that IVR10 had a 2.12-fold reduction in sensitivity to IVM compared to N2B. Additionally, cross-resistance assessment showed that IVR10 exhibited decreased sensitivity to moxidectin (MOX) and eprinomectin (EPR) relative to N2B. Further investigation conducted on Haemonchus contortus revealed significant differences in drug potency between susceptible and resistant isolates, with MOX demonstrating the highest efficacy. Resistance factors (RF) highlighted the substantial resistance of the isolate collected in a farm with EPR-treatment failure. The WMA effectively discriminated susceptible from resistant isolates in both C. elegans and H. contortus. Our findings demonstrate, for the first time, the relevance of WMA as a phenotypic assay for detecting ML resistance in nematodes by measuring their motility response. This research sheds light on a novel approach for monitoring drug resistance, vital for effective parasite management strategies.https://doi.org/10.1038/s41598-025-02866-3Macrocyclic lactonesMotilityCaenorhabditis elegansHaemonchus contortusWMicrotracker
spellingShingle Mélanie Alberich
Marie Garcia
Julie Petermann
Clara Blancfuney
Sophie Jouffroy
Philippe Jacquiet
Anne Lespine
Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay
Scientific Reports
Macrocyclic lactones
Motility
Caenorhabditis elegans
Haemonchus contortus
WMicrotracker
title Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay
title_full Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay
title_fullStr Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay
title_full_unstemmed Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay
title_short Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay
title_sort evaluation of nematode susceptibility and resistance to anthelmintic drugs with a wmicrotracker motility assay
topic Macrocyclic lactones
Motility
Caenorhabditis elegans
Haemonchus contortus
WMicrotracker
url https://doi.org/10.1038/s41598-025-02866-3
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