Role of the HG1 gene in larval movement and response to moxidectin in Haemonchus contortus

• Main Author: Zhou, Shufeng, 1965-
• Format: Others
• Language: en
• Published: McGill University 2006
• Subjects: Haemonchus contortus > Molecular genetics.; Haemonchus contortus > Larvae.; Avermectins.; Drug resistance.
• Online Access: http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=99215

Haemonchus contortus is a nematode parasite that infects sheep and goats, and other ruminants, causing substantial economic loss throughout the world. Anthelmintic drugs are the primary method to control these parasites; however, resistance to all broad spectrum anthelmintics, including the newer avermectins and milbemycins, has been developing rapidly in nematode parasites. The mechanism of avermectin resistance is unknown, but previous studies indicate that at least four genes are involved. A single nucleotide polymorphism (SNP) in the Haemonchus contortus HG1 gene has been linked to ivermectin (IVM) and moxidectin (MOX) resistance. This gene encodes a GABA-gated chloride channel thought to control body muscle movement in H. contortus and mediates IVM and MOX paralysis. The present study was designed to determine whether there is an association between variation in this gene and the ability of H. contortus larvae to move in the presence and absence of MOX. The present study also investigated the difference between a laboratory strain (PF23) and an ivermectin resistant field strain (VHR29). Fourteen different MOX concentrations (ranging from 0.078nm to 156uM) and at least 200 third stage (L3) larvae for each concentration were investigated for each strain. An L3 larval motility assay was used to determine the movement phenotype of individual larva. Pyrosequencing was used to identify the genotype of each individual larva. The present study found that in the PF23 strain, the resistant heterozygote genotype GA protected against the effects of MOX, and that the protection was dose dependent. This was not the case, however, in the VHR29 field strain. For this strain, no protective effect of the HG1 variation was observed with moxidectin treatment. One reason for this may be that field strains are selected under higher drug pressure which favors a monogenic response. The present study has shown that while the HG1 variation does play a role in larval movement and resistance to MOX, this effect may be minor compared to other effects selected in the field.