The effect of the microtubule inhibitor tubulozole-C on the tegument of triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica.
The benzimidazole derivative, triclabendazole is the main drug used against Fasciola hepatica, although its precise mode of action remains to be fully determined. Previous studies have suggested that triclabendazole acts as a microtubule inhibitor in the same manner as tubulozole-C. Consequently, flukes from triclabendazole-susceptible and triclabendazole-resistant isolates were treated with tubulozole-C (1x10(-6 )M) in vitro and changes in tegumental morphology and tubulin distribution within the tegument were monitored by scanning and transmission electron microscopy, together with tubulin immunocytochemistry. Tubulozole-C caused severe disruption within the tegument of triclabendazole-susceptible flukes. Tubulin immunoreactivity diminished within the tegumental syncytium of the triclabendazole-susceptible flukes following treatment with tubulozole-C. In contrast, tubulozole-C caused only minor disruption of the tegument in triclabendazole-resistant F. hepatica and did not significantly alter the pattern of tubulin immunostaining within the tegumental syncytium. The results of the present study indicate that tubulozole-C and triclabendazole share the same target molecule and that triclabendazole-resistant flukes are also cross-resistant to tubulozole-C.
Robinson
Mark W
MW
Department of Veterinary Science, The Queen's University of Belfast, Stoney Road, Stormont, BT4 3SD Belfast, Northern Ireland.
Trudgett
Alan
A
Hoey
Elizabeth M
EM
Fairweather
Ian
I
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004148:Dioxolanes / Q000494:pharmacology*; D004351:Drug Resistance; D005210:Fasciola hepatica / Q000187:drug effects* / Q000648:ultrastructure; D005211:Fascioliasis / Q000469:parasitology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D021261:Parasitic Sensitivity Tests; D051381:Rats; D000077682:Triclabendazole; D014404:Tubulin / Q000378:metabolism
D000980:Antiplatyhelmintic Agents; D001562:Benzimidazoles; D004148:Dioxolanes; D014404:Tubulin; D000077682:Triclabendazole; C040422:tubulazole