ArticlePLoS neglected tropical diseases2018
Discovery of genomic intervals that underlie nematode responses to benzimidazoles.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
- Article
- Evaluating beta-tubulin variants as predictors of benzimidazole resistance across Caenorhabditis nematodes.PLoS pathogens · 2026Article
- Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.PLoS pathogens · 2025Article
- Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans.PLoS pathogens · 2024Article
- Quantitative tests of albendazole resistance in beta-tubulin mutants.bioRxiv : the preprint server for biology · 2024Article
- Altered larval activation response associated with multidrug resistance in the canine hookwormParasitology · 2024Article
- CaeNDR, the Caenorhabditis Natural Diversity Resource.Nucleic acids research · 2024Article
- Beyond the reference: gene expression variation and transcriptional response to RNA interference in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2023Article
- High-fidelity encoding of mechanostimuli by tactile food-sensing neurons requires an ensemble of ion channels.Cell reports · 2023Article
- Cryptic genetic variation of expression quantitative trait locus architecture revealed by genetic perturbation in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2023Article
- Variation in anthelmintic responses are driven by genetic differences among diverse C. elegans wild strains.PLoS pathogens · 2023Article
- Beyond the reference: gene expression variation and transcriptional response to RNAi inbioRxiv : the preprint server for biology · 2023Article
- Article
- Pharmacological Profiling of a Brugia malayi Muscarinic Acetylcholine Receptor as a Putative Antiparasitic Target.Antimicrobial agents and chemotherapy · 2023Article
- Praziquantel inhibits Caenorhabditis elegans development and species-wide differences might be cct-8-dependent.PloS one · 2023Article
- Article
- Interactions of Caenorhabditis elegans β-tubulins with the microtubule inhibitor and anthelmintic drug albendazole.Genetics · 2022Article
- Anthelmintic Effect ofMolecules (Basel, Switzerland) · 2022Article
- Review
- From QTL to gene: C. elegans facilitates discoveries of the genetic mechanisms underlying natural variation.Trends in genetics : TIG · 2021Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole target resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control.
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Registered trials
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