A dyf-7 haplotype causes sensory neuron defects and is associated with macrocyclic lactone resistance worldwide in the nematode parasite Haemonchus contortus |
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| Affiliation: | 1. Institute of Parasitology, 21111 Lakeshore, McGill University, Ste-Anne de Bellevue H9X3V9, Canada;2. Department of Biology, 1205 Ave. Docteur Penfield, McGill University, Montreal H3A1B1, Canada;1. CSIRO Agriculture Flagship, Queensland Bioscience Precinct, University of Queensland, Brisbane, Australia;2. School of Veterinary Science, University of Queensland, Gatton, Australia;3. School of Veterinary Science, University of Melbourne, Werribee, Victoria, Australia;1. Department of Biology, Brandon University, 270-18th Street, Brandon, Manitoba R7A 6A9, Canada;2. Institute of Parasitology, McGill University, 21-111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec H9X 3V9, Canada;1. Institute of Parasitology, Macdonald Campus, McGill University, 21, 111 Lakeshore Road, Ste-Anne-de-Bellevue, QC H9X3V9, Canada;2. College of Veterinary Medicine, Auburn University, 1500 Wire Rd, Auburn, AL 36849, USA;1. Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Germany;2. Faculty of Veterinary Science, University of Sydney, Australia;3. Microbial Screening Technologies (MST), Smithfield, Australia;4. School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, 2650 NSW, Australia |
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| Abstract: | Heavy reliance on macrocyclic lactones to treat parasitic nematodes has resulted in the evolution of widespread drug resistance that threatens human and animal health. Management strategies have been proposed that would slow the rise of resistance, however testing these strategies has been hampered by the lack of identified strong-effect resistance markers in parasites. We show that the Caenorhabditis elegans gene Cel_dyf-7, necessary for amphid sensory neuron development, also confers macrocyclic lactone sensitivity. In the sheep parasite Haemonchus contortus: (i) strains selected for macrocyclic lactone resistance were enriched in a Hco_dyf-7 haplotype that was rare in the drug-naïve population, (ii) the resistant haplotype correlated with the sensory neuron defects, and (iii) the resistant haplotype was associated with decreased Hco_dyf-7 expression. Resistant field isolates of H. contortus from five continents were enriched for the resistant haplotype, demonstrating the relevance of the Hco_dyf-7 haplotype to practise and indicating that it is a locus of strong effect. Hemizygosity resulting from sex linkage of dyf-7 likely contributes to the rise of resistance in treated populations. |
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| Keywords: | Ivermectin Macrocyclic-lactone Resistance Nematodes Amphids |
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