DIFFERENTIAL STABILITY OF THE BENZIMIDAZOLE (BZ) TUBULIN COMPLEX IN BZ-RESISTANT AND BZ-SUSCEPTIBLE ISOLATES OF HAEMONCHUS-CONTORTUS AND TRICHOSTRONGYLUS-COLUBRIFORMIS

The binding of [H-3]mebendazole ([H-3]MBZ) to tubulin from BZ-susceptible (BZ-S) and BZ-resistant (BZ-R) isolates of Haemonchus contortus and Trichostrongylus colubriformis was investigated using charcoal extraction and gel filtration techniques. The amount of [H-3]MBZ bound at infinite free ligand concentration (B(max)) was significantly reduced for the BZ-R isolate compared with the BZ-S isolate in both species when assayed by charcoal extraction. However, B(max) was increased to comparable levels for both BZ-S and BZ-R isolates of each species when assayed by the less stringent gel filtration technique. These results indicate that the BZ-tubulin interaction in trichostrongylid nematodes is comprised of a minimum of two components. As similar levels of total [H-3]MBZ binding were observed for both BZ-S and BZ-R isolates of each species when assayed by gel filtration, it is suggested that the reduction in the pseudo-irreversible BZ binding component in BZ-R isolates results in an increase in the level of reversible BZ binding and therefore provides a survival advantage to BZ-R nematodes.