Haemonchus contortus: Selection at a Glutamate-Gated Chloride Channel Gene in Ivermectin- and Moxidectin-Selected Strains

Abstract

Blackhall, W. J., Pouliot, J.-F., Prichard, R. K., and Beech, R. N. 1998.Haemonchus contortus: Selection at a glutamate-gated chloride channel gene in ivermectin- and moxidectin-selected strains.Experimental Parasitology90, 42–48. Anthelmintic resistance in nematode parasites of livestock is a serious problem worldwide. Ivermectin, an avermectin, and moxidectin, a milbemycin, are potent endectocides commonly used to control these parasites. The proposed mode of action of avermectins and possibly the milbemycins involves the binding of the drug to the α-subunit of a glutamate-gated chloride channel, which opens or potentiates gating of the channel and leads to the hyperpolarization of the target neuromuscular cell. Glutamate gates the channel by binding to the β-subunit. We have cloned a fragment of a putative α-subunit gene fromHaemonchus contortus.The sequence of the beta subunit is available from GenBank. Genetic variability of this fragment was analysed by single-strand conformation polymorphism in five strains ofH. contortus: two strains passaged without drug selection, two strains selected with ivermectin, and one strain selected with moxidectin. One allele of the putative α-subunit gene appeared to be associated with resistance to the drugs, increasing in frequency in the three drug-selected strains relative to the unselected strains. Another allele appeared to be associated with susceptibility, decreasing in frequency in the three drug-selected strains relative to the unselected strains. A similar analysis of the β-subunit gene showed no significant differences in allele frequencies between the unselected and drug-selected strains. Our findings suggest a correlation between changes in allele frequencies of the putative α-subunit gene and resistance to ivermectin and moxidectin.