Differential expression of liver fluke 尾-tubulin isotypes at selected life cycle stages

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• 作者：Marc-Aurel Fuchs ; Louise A. Ryan ; Emma L. Chambers ; Catherine M. Moore ; Ian Fairweather ; Alan Trudgett ; David J. Timson ; Gerry P. Brennan ; Elizabeth M. Hoey
• 关键词：Fasciola hepatica ; Anthelmintic resistance ; Tubulin isotype ; Microtubule
• 刊名：International Journal for Parasitology
• 出版年：December, 2013
• 年：2013
• 卷：43
• 期：14
• 页码：1133-1139
• 全文大小：1096 K

文摘

We have shown that Fasciola hepatica expresses at least six 尾-tubulins in the adult stage of its life cycle, designated F.hep-尾-tub1-6 (Ryan et al., 2008). Here we show that different complements of tubulin isotypes are expressed in different tissues and at different life cycle stages; this information may inform the search for novel anthelmintics. The predominant (as judged by quantitative PCR) isotype transcribed at the adult stage was F.hep-尾-tub1 and immunolocalisation studies revealed that this isotype occurred mainly in mature spermatozoa and vitelline follicles. Quantitative PCR indicated that changes occurred in the transcription levels of 尾-tubulin isotypes at certain life cycle stages and may be of importance in the efficacy of benzimidazole-based anthelmintic drugs, but there were no significant differences between the triclabendazole-susceptible Leon isolate and the triclabendazole-resistant Oberon isolate in the transcription levels of each of the isotypes. When three well-characterised isolates with differing susceptibilities to triclabendazole were compared, only one amino acid change resulting from a homozygous coding sequence difference (Gly269Ser) in isotype 4 was observed. However, this change was not predicted to alter the overall structure of the protein. In conclusion, these findings indicate that there is tissue-specific expression of tubulin isotypes in the liver fluke but the development of resistance to triclabendazole is not associated with changes in its presumed target molecule.