HAEMONCHUS-CONTORTUS - SELECTION AT A GLUTAMATE-GATED CHLORIDE CHANNEL GENE IN IVERMECTIN-SELECTED AND MOXIDECTIN-SELECTED STRAINS

Anthelmintic resistance in nematode parasites of livestock is a seriou s problem worldwide. Ivermectin, an avermectin, and moxidectin, a milb emycin, are potent endectocides commonly used to control these parasit es. The proposed mode of action of avermectins and possibly the milbem ycins involves the binding of the drug to the alpha-subunit of a gluta mate-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 P-subunit. We hav e cloned a fragment of a putative cc-subunit gene from Haemonchus cont ortus. The sequence of the beta subunit is available from GenBank. Gen etic variability of this fragment was analysed by single-strand confor mation polymorphism in five strains of H. contortus: two strains passa ged without drug selection, two strains selected with ivermectin, and one strain selected with moxidectin. One allele of the putative cr sub unit gene appeared to be associated with resistance to the drugs, incr easing in frequency in the three drug-selected strains relative to the unselected strains. Another allele appeared to be associated with sus ceptibility, decreasing in frequency in the three drug-selected strain s relative to the unselected strains. A similar analysis of the P-subu nit gene showed no significant differences in allele frequencies betwe en the unselected and drug-selected strains. Our findings suggest a co rrelation between changes in allele frequencies of the putative a-subu nit gene and resistance to ivermectin and moxidectin. (C) 1998 Academi c Press.