Comparative proteomic analysis of Triclabendazole response in the liver fluke Fasciola hepatica

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dc.contributor.author Chemale, Gustavo
dc.contributor.author Perally, S.
dc.contributor.author LaCourse, E. James
dc.contributor.author Prescott, Mark C.
dc.contributor.author Jones, L. M.
dc.contributor.author Ward, Deborah
dc.contributor.author Meany, Myles
dc.contributor.author Hoey, Elizabeth
dc.contributor.author Brennan, Gerard P.
dc.contributor.author Fairweather, Ian
dc.contributor.author Trudgett, Alan
dc.contributor.author Brophy, P. M.
dc.date.accessioned 2011-06-01T13:17:53Z
dc.date.available 2011-06-01T13:17:53Z
dc.date.issued 2010-07-19
dc.identifier.citation Chemale , G , Perally , S , LaCourse , E J , Prescott , M C , Jones , L M , Ward , D , Meany , M , Hoey , E , Brennan , G P , Fairweather , I , Trudgett , A & Brophy , P M 2010 , ' Comparative proteomic analysis of Triclabendazole response in the liver fluke Fasciola hepatica ' Journal of Proteome Research , vol 9 , no. 10 , pp. 4940-4951 . en
dc.identifier.issn 1535-3907
dc.identifier.other PURE: 163117
dc.identifier.other dspace: 2160/6881
dc.identifier.uri http://hdl.handle.net/2160/6881
dc.description Chemale, G., Perally, S., LaCourse, E.J., Prescott, M.C., Jones, L.M., Ward, D., Meaney, M., Hoey, E., Brennan, G.P., Fairweather, I., Trudgett, A., Brophy, P.M. (2010). Comparative proteomic analysis of triclabendazole response in the liver fluke Fasciola hepatica.  Journal of Proteome Research, 9, (10), 4940-4951. IMPF: 05.46 The parasitic flatworm Fasciola hepatica causes major economic and welfare issues to the livestock industry worldwide. There are no vaccines and increasing reports of resistance to Triclabendazole (TCBZ), the only drug available to target pathogenic young fluke. This paper used proteomic approaches in defined isolates to increase understanding of TCBZ response and identify potential biomarkers of resistance. Contributed to experimental design (33%) and manuscript preparation (25%) and PI of joint BBSRC / DEFRA programme that primarily funded work. The findings are being translated via Welsh Assembly Government, Meat Promotion Wales (HCC) and BBSRC Pathfinder funding. Sponsorship: BBSRC / DeLiver project (FOOD-CT-2005-023025). en
dc.description.abstract Control of Fasciola hepatica infections of livestock in the absence of vaccines depends largely on the chemical triclabendazole (TCBZ) because it is effective against immature and adult parasites. Overdependence on a single drug and improper application is considered a significant factor in increasing global reports of fluke resistant to TCBZ. The mode(s) of action and biological target(s) of TCBZ are not confirmed, delaying detection and the monitoring of early TCBZ resistance. In this study, to further understand liver fluke response to TCBZ, the soluble proteomes of TCBZ-resistant and TCBZ-susceptible isolates of F. hepatica were compared with and without in vitro exposure to the metabolically active form of the parent drug triclabendazole sulphoxide (TCBZ-SO), via two-dimensional gel electrophoresis (2-DE). Gel image analysis revealed proteins displaying altered synthesis patterns and responses both between isolates and under TCBZ-SO exposure. These proteins were identified by mass spectrometry supported by a F. hepatica expressed sequence tag (EST) data set. The TCBZ responding proteins were grouped into three categories; structural proteins, energy metabolism proteins, and “stress” response proteins. This single proteomic investigation supported the reductionist experiments from many laboratories that collectively suggest TCBZ has a range of effects on liver fluke metabolism. Proteomics highlighted differences in the innate proteome profile of different fluke isolates that may influence future therapy and diagnostics design. Two of the TCBZ responding proteins, a glutathione transferase and a fatty acid binding protein, were cloned, produced as recombinants, and both found to bind TCBZ-SO at physiologically relevant concentrations, which may indicate a role in TCBZ metabolism and resistance. Keywords: Fasciola hepatica; triclabendazole; 2-DE; glutathione transferase; fatty acid binding protein en
dc.format.extent 12 en
dc.language.iso eng
dc.relation.ispartof Journal of Proteome Research en
dc.subject Fasciola hepatica en
dc.subject triclabendazole en
dc.subject 2-DE en
dc.subject glutathione transferase en
dc.subject fatty acid binding protein en
dc.title Comparative proteomic analysis of Triclabendazole response in the liver fluke Fasciola hepatica en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1021/pr1000785
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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