title: Association of ion-channel genotype and macrocyclic lactone sensitivity traits in Haemonchus contortus.
abstract: Resistance to macrocyclic lactones in the strongylid parasite of sheep, Haemonchus contortus, is associated with specific alleles of several genes, including those encoding ligand-gated chloride-channels. While previous functional studies of the ion-channels encoded by these resistant alleles have revealed alterations in ligand binding and response to the anthelmintics, we still do not know how these alleles are contributing to resistance in vivo. To understand the phenomenon of anthelmintic resistance in detail we need to link changes in the genes of individual parasites with their ability to resist the effects of anthelmintic exposure. We have determined the genotype of individual adult and larval H. contortus with respect to the glc-5 and lgc-37 genes linked with macrocyclic lactone resistance. In these same individuals, we measured feeding and movement, two characteristics targeted by the drug, which are believed to contribute to parasite killing. Both genes are linked with altered behavior in the absence of drug, providing evidence that genetic resistance may be associated with alterations in parasite biology. In the presence of macrocyclic lactones, both genes are associated with a degree of protection against drug action. Whether this protection may be effective under the application of anthelmintic as part of normal farm practice and whether this could explain the evolution of resistance remain unclear.
authors.affiliation: Institute of Parasitology, Macdonald College, McGill University, 21,111 Lakeshore Road, Ste Anne de Bellevue, Quebec, H9X 3V9, Canada. robin.beech@mcgill.ca
authors.forename: Robin
authors.initials: R
authors.lastname: Beech
authors.forename: Nancy
authors.initials: N
authors.lastname: Levitt
authors.forename: Mathieu
authors.initials: M
authors.lastname: Cambos
authors.forename: Shufeng
authors.initials: S
authors.lastname: Zhou
authors.forename: Sean G
authors.initials: SG
authors.lastname: Forrester
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005247:Feeding Behavior / Q000187:drug effects; D005838:Genotype; D006189:Haemonchus / Q000187:drug effects* / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics*; D007559:Ivermectin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D018942:Macrolides / Q000494:pharmacology; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D012756:Sheep / Q000469:parasitology
chemical_list: D000871:Anthelmintics; D018509:DNA, Helminth; D015801:Helminth Proteins; D007473:Ion Channels; D007783:Lactones; D018942:Macrolides; D007559:Ivermectin; C027837:moxidectin