The susceptibility analysis of Echinococcus multilocularis protoscoleces tubulin to mebendazole and RNA interference

Abstract

ABSTRACTAlveolar echinococcosis, caused by the larval (metacestode) stage of the tapeworm Echinococcus multilocularis, is a lethal parasitosis of the liver prevalent in the Northern Hemisphere. For chemotherapy the benzimidazole derivatives mebendazole and albendazole were introduced, which were found to disrupt the microtubules by inhibition of the polymerization of tubulin into microtubules, and β-tubulin was determined to be the drug target molecule. In the present study, we evaluated the chemosensitivity of E. multilocularis protoscoleces tubulin to mebendazole and RNA interference in vitro, and to explore whether the molecular level and ultrastructure of E. multilocularis protoscoleces microtubules change post-mebendazole and RNA interference. We identified that mebendazole is parasitostatic to E. multilocularis protoscoleces through suppression the tubulin expression and change the flame cell morphology in molecular level, besides RNA interference indicated that β 2 tubulin is probably one of the vital tubulin gene to form the flame cell and the protonephridial system tubules (collective tubes) of E. multilocularis protoscoleces. Molecular level and ultrastructure detection were performed by reverse transcription-PCR, western blotting and transmission electron microscope. The RNA interference would be probably as a parasitocidal method to disrupt the survival of PSCs, extend that the relevant tubulin maybe as potential target for drug development against AE.