4.5 Article

A dyf-7 haplotype causes sensory neuron defects and is associated with macrocyclic lactone resistance worldwide in the nematode parasite Haemonchus contortus

期刊

INTERNATIONAL JOURNAL FOR PARASITOLOGY
卷 44, 期 14, 页码 1063-1071

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.ijpara.2014.08.005

关键词

Ivermectin; Macrocyclic-lactone; Resistance; Nematodes; Dyf-7; Haemonchus contortus; Caenorhabditis elegans; Amphids

资金

  1. Natural Sciences and Engineering Research Council of Canada, Canada
  2. Fonds de Recherche du Quebec-Nature et Technologie, Quebec, Canada
  3. Ministere de l'Economie, de l'Innovation et des Exportations- Programme de Soutien la Recherche, Soutien des Initiatives Internationales de Recherche et d'Innovation, Quebec, Canada
  4. Quebec Centre for Host-Parasite Interactions, Canada
  5. National Institutes of Health, USA, Office of Research Infrastructure Programs [P40 OD010440]

向作者/读者索取更多资源

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-naive 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. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

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