Allozyme analysis of Haemonchus contortus resistant and susceptible to anthelmintics, with an indication of dipeptidases associated with resistance

In an attempt to investigate the genetic and biochemical causes underlying resistance to anthelmintics, the trichostrongylid nematode Haemonchus contortus was examined by an allozymic analysis of nine candidate geneenzyme systems. Two strains resistant to benzimidazoles, two multidrug-resistant strains, and three strains susceptible to anthelmintics isolated from three continents were examined by isoelectric focusing. Two enzymes (mannose phosphate isomerase and peptidase-D) had polymorphic patterns. The peptidase-D zymograms indicated an association with the selection for resistance. Susceptible isolates gave more complex patterns due to the formation of a heterodimer controlled by the two active loci, whereas in resistant isolates, only a single locus with one electromorph was responsible for the profiles. A possible link between dipeptidases and the acquisition of resistance through the turnover of proteinrich collagen, and changes in membrane-associated genes that influence drug efflux, are discussed.