Alberich Mélanie, Garcia Marie, Petermann Julie, Blancfuney Clara, Jouffroy Sophie, Jacquiet Philippe, Lespine Anne
INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
IHAP, Université de Toulouse, INRAE, ENVT, Toulouse, France.
Sci Rep. 2025 May 23;15(1):17968. doi: 10.1038/s41598-025-02866-3.
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.
放牧反刍动物遭受各种蠕虫感染，尤其是由胃肠道线虫（GIN）寄生虫引起的感染，这些感染对它们的健康和生产力有相当大的影响。为了治疗这些感染，大环内酯（ML）驱虫药的大量使用导致全球出现了耐药寄生虫种群。检测耐药性的标准方法，即粪便虫卵计数减少试验（FECRT），容易产生误解，导致有缺陷的管理决策，破坏寄生虫控制工作。因此，迫切需要在野外寄生虫中采用可靠的耐药性检测方法。我们研究了WMicrotracker运动分析（WMA）在ML耐药性评估中尚未探索的潜力。该分析首先比较了野生型布里斯托尔N2（N2B）、伊维菌素选择型（IVR10）和nhr-8功能缺失型（AE501；nhr8(ok186)）秀丽隐杆线虫菌株对伊维菌素（IVM）的敏感性。剂量反应曲线表明，与N2B相比，IVR10对IVM的敏感性降低了2.12倍。此外，交叉耐药性评估表明，与N2B相比，IVR10对莫西菌素（MOX）和埃普利诺菌素（EPR）的敏感性降低。对捻转血矛线虫的进一步研究表明，敏感和耐药分离株之间的药物效力存在显著差异，其中MOX的疗效最高。耐药因子（RF）突出了在一个农场收集的、对EPR治疗无效的分离株的高度耐药性。WMA有效地区分了秀丽隐杆线虫和捻转血矛线虫中的敏感和耐药分离株。我们的研究结果首次证明了WMA作为一种通过测量线虫运动反应来检测ML耐药性的表型分析方法的相关性。这项研究揭示了一种监测耐药性的新方法，这对有效的寄生虫管理策略至关重要。
