Genomic landscape of drug response reveals novel mediators of anthelmintic resistance

S.R. Doyle, R Laing, David Bartley, A. Morrison, N. Holroyd, K. Maitland , A. Antonopoulos, C. Britton, Umer Chaudhry, I. Flis , S. Howell, J. McIntyre, J.S. Gilleard, A. Tait , B. Mable , R. Kaplan, Neil Sargison, C. Britton, M. Berriman , E DevaneyJ. Cotton

Research output: Contribution to journalArticlepeer-review


Like other pathogens, parasitic helminths can rapidly evolve resistance to drug treatment. Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to tracking its spread and improving the efficacy and sustainability of parasite control. Here, we use an in vivo genetic cross between drug-susceptible and multi-drug-resistant strains of Haemonchus contortus in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies new alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor cky-1 in ivermectin resistance. This gene is within a locus under selection in ivermectin-resistant populations worldwide; expression analyses and functional validation using knockdown experiments support that cky-1 is associated with ivermectin survival. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode and identifies variants for the development of molecular diagnostics to combat drug resistance in the field.

Original languageEnglish
Article number111522
Pages (from-to)1-24
Number of pages24
JournalCell Reports
Issue number3
Early online date18 Oct 2022
Publication statusPublished - 18 Oct 2022


  • Anthelmintics/pharmacology
  • Benzimidazoles
  • Drug Resistance/genetics
  • Genomics
  • Ivermectin/pharmacology
  • Levamisole
  • Transcription Factors


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