ArticlePLoS pathogens2022
Transcriptomic analyses implicate neuronal plasticity and chloride homeostasis in ivermectin resistance and response to treatment in a parasitic nematode.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Preliminary survey of anthelmintic efficacy in selected smallholder sheep and goat flocks in Sarawak, Malaysia.Tropical animal health and production · 2026Article
- P-glycoproteins and amphids: a two-stage trajectory of ivermectin resistance in Caenorhabditis elegans.International journal for parasitology. Drugs and drug resistance · 2026Article
- Current issues in heartworm chemotherapy.Parasites & vectors · 2026Review
- Critical role of P-Glycoprotein-9 in ivermectin tolerance in nematodes.PLoS pathogens · 2026Article
- Metabolomic and proteomic differences in susceptible and benzimidazole-resistant adult females and males of Haemonchus contortus.Veterinary research · 2025Article
- Analyses of emerging macrocyclic lactone resistance: Speed and signature of ivermectin and moxidectin selection and evidence of a shared genetic locus.PLoS pathogens · 2025Article
- Efficacy of fenbendazole against gastrointestinal nematodes in naturally infected goats in Maputo Province, Mozambique using in vivo, in vitro and molecular assessment.International journal for parasitology. Drugs and drug resistance · 2025Article
- Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.PLoS pathogens · 2025Article
- Article
- Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans.PLoS pathogens · 2024Article
- Altered larval activation response associated with multidrug resistance in the canine hookwormParasitology · 2024Article
- Getting around the roundworms: Identifying knowledge gaps and research priorities for the ascarids.Advances in parasitology · 2024Article
- Gene co-expression network analysis reveal core responsive genes in Parascaris univalens tissues following ivermectin exposure.PloS one · 2024Article
- Ancient diversity in host-parasite interaction genes in a model parasitic nematode.Nature communications · 2023Article
- Recent Advances in the Control of Endoparasites in Ruminants from a Sustainable Perspective.Pathogens (Basel, Switzerland) · 2023Article
- The turkey ascarid, Ascaridia dissimilis, as a model genetic system.International journal for parasitology · 2023Article
- Pharmacokinetic and pharmacodynamic considerations for treating sarcoptic mange with cross-relevance to Australian wildlife.International journal for parasitology. Drugs and drug resistance · 2023Review
- Assembly and Analysis ofPathogens (Basel, Switzerland) · 2023Article
- A major locus confers triclabendazole resistance in Fasciola hepatica and shows dominant inheritance.PLoS pathogens · 2023Article
- Transcriptome profile of halofuginone resistant and sensitive strains ofFrontiers in microbiology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The antiparasitic drug ivermectin plays an essential role in human and animal health globally. However, ivermectin resistance is widespread in veterinary helminths and there are growing concerns of sub-optimal responses to treatment in related helminths of humans. Despite decades of research, the genetic mechanisms underlying ivermectin resistance are poorly understood in parasitic helminths. This reflects significant uncertainty regarding the mode of action of ivermectin in parasitic helminths, and the genetic complexity of these organisms; parasitic helminths have large, rapidly evolving genomes and differences in evolutionary history and genetic background can confound comparisons between resistant and susceptible populations. We undertook a controlled genetic cross of a multi-drug resistant and a susceptible reference isolate of Haemonchus contortus, an economically important gastrointestinal nematode of sheep, and ivermectin-selected the F2 population for comparison with an untreated F2 control. RNA-seq analyses of male and female adults of all populations identified high transcriptomic differentiation between parental isolates, which was significantly reduced in the F2, allowing differences associated specifically with ivermectin resistance to be identified. In all resistant populations, there was constitutive upregulation of a single gene, HCON_00155390:cky-1, a putative pharyngeal-expressed transcription factor, in a narrow locus on chromosome V previously shown to be under ivermectin selection. In addition, we detected sex-specific differences in gene expression between resistant and susceptible populations, including constitutive upregulation of a P-glycoprotein, HCON_00162780:pgp-11, in resistant males only. After ivermectin selection, we identified differential expression of genes with roles in neuronal function and chloride homeostasis, which is consistent with an adaptive response to ivermectin-induced hyperpolarisation of neuromuscular cells. Overall, we show the utility of a genetic cross to identify differences in gene expression that are specific to ivermectin selection and provide a framework to better understand ivermectin resistance and response to treatment in parasitic helminths.
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Registered trials
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