Differential stability of the benzimidazole (BZ)-tubulin complex in BZ-resistant and BZ-susceptible isolates of Haemonchus contortus and Trichostrongylus colubriformis.
The binding of [3H]mebendazole ([3H]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 [3H]MBZ bound at infinite free ligand concentration (Bmax) was significantly reduced for the BZ-R isolate compared with the BZ-S isolate in both species when assayed by charcoal extraction. However, Bmax 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 [3H]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.
Russell
G J
GJ
Department of Veterinary Pathology, University of Sydney, New South Wales, Australia.
Lacey
E
E
D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance; D004355:Drug Stability; D006189:Haemonchus / Q000187:drug effects* / Q000378:metabolism; D014254:Trichostrongylus / Q000187:drug effects*; D014404:Tubulin / Q000378:metabolism*
D001562:Benzimidazoles; D014404:Tubulin; C031000:benzimidazole