In depth analysis of the tubulin family in Fasciola hepatica: A combined bioinformatics and sub-proteomic approach.


M K Wilamska- Chyrczakowska1; C F Collett2; D Cutress2; R Stuart3; R M Morphew2
1 Aberystwyth University, UK;  2 Aberystwyth University - IBERS, UK;  3 Hybu Cig Cymru Meat Promotion Wales, UK


The parasitic trematode Fasciola hepatica infects many host organisms including sheep, cattle and humans. F. hepatica is responsible for major economical and veterinary health losses across the globe and such losses include high costs of drug treatment and farm management strategies, reduction in milk and wool production, growth rates and fertility. Triclabendazole (TCBZ), which targets both juvenile and adult forms of F. hepatica, is the current drug of choice, yet resistance to TCBZ has developed causing further control challenges. The mechanism of TCBZ action is currently still unknown which thus prevents monitoring resistance in the field and how it has developed.

A significant body of evidence points towards tubulins as a target of TCBZ action. At present our understanding of the tubulin family is limited to 5 alpha and 6 beta tubulins. The current work aims to comprehensively map the F. hepatica tubulin superfamily family using bioinformatics, incorporating the latest genome information, combined with a sub proteomics approach. Both α-tubulins and β-tubulins are expanded from the previously known 5 and 6 isoforms respectively. This includes variations in tubulin profiles for TCBZ resistant and susceptible isolates. Using sub-proteomics we have examined the expressed tubulin isoforms. Finally, we are investigating the role of microtubule-associated proteins (MAPs) and TCBZ mode of action through the purification of native microtubules. MAPs are likely altered following TCBZ exposure and thus warrant investigation to help elucidate TCBZ mode of action.

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