Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics

<i>Fasciola hepatica</i>, the causative agent of fasciolosis, is a global threat to public health, animal welfare, agricultural productivity, and food security. In the ongoing absence of a commercial vaccine, independent emergences of anthelmintic-resistant parasite populations worldwide...

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Main Authors: Clare F. Collett, Russell M. Morphew, David Timson, Helen C. Phillips, Peter M. Brophy
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/15/3477
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author Clare F. Collett
Russell M. Morphew
David Timson
Helen C. Phillips
Peter M. Brophy
author_facet Clare F. Collett
Russell M. Morphew
David Timson
Helen C. Phillips
Peter M. Brophy
author_sort Clare F. Collett
collection DOAJ
description <i>Fasciola hepatica</i>, the causative agent of fasciolosis, is a global threat to public health, animal welfare, agricultural productivity, and food security. In the ongoing absence of a commercial vaccine, independent emergences of anthelmintic-resistant parasite populations worldwide are threatening the sustainability of the few flukicides presently available, and particularly triclabendazole (TCBZ) as the drug of choice. Consequently, prognoses for future fasciolosis control and sustained TCBZ application necessitate improvements in diagnostic tools to identify anthelmintic efficacy. Previously, we have shown that proteomic fingerprinting of <i>F. hepatica</i> excretory/secretory (ES) products offered new biomarkers associated with in vitro TCBZ-sulfoxide (SO) recovery or death. In the current paper, two of these biomarkers (calreticulin (CRT) and triose phosphate isomerase (TPI)) were recombinantly expressed and evaluated to measure TCBZ efficacy via a novel approach to decipher fluke molecular phenotypes independently of molecular parasite resistance mechanism(s), which are still not fully characterised or understood. Our findings confirmed the immunoreactivity and diagnostic potential of the present target antigens by sera from TCBZ-susceptible (TCBZ-S) and TCBZ-resistant (TCBZ-R) <i>F. hepatica</i> experimentally infected sheep.
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spelling doaj.art-58523ece228b4e2cbca4141aa17d81d92023-11-20T08:33:06ZengMDPI AGMolecules1420-30492020-07-012515347710.3390/molecules25153477Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy DiagnosticsClare F. Collett0Russell M. Morphew1David Timson2Helen C. Phillips3Peter M. Brophy4Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA, UKInstitute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA, UKSchool of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UKInstitute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA, UKInstitute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA, UK<i>Fasciola hepatica</i>, the causative agent of fasciolosis, is a global threat to public health, animal welfare, agricultural productivity, and food security. In the ongoing absence of a commercial vaccine, independent emergences of anthelmintic-resistant parasite populations worldwide are threatening the sustainability of the few flukicides presently available, and particularly triclabendazole (TCBZ) as the drug of choice. Consequently, prognoses for future fasciolosis control and sustained TCBZ application necessitate improvements in diagnostic tools to identify anthelmintic efficacy. Previously, we have shown that proteomic fingerprinting of <i>F. hepatica</i> excretory/secretory (ES) products offered new biomarkers associated with in vitro TCBZ-sulfoxide (SO) recovery or death. In the current paper, two of these biomarkers (calreticulin (CRT) and triose phosphate isomerase (TPI)) were recombinantly expressed and evaluated to measure TCBZ efficacy via a novel approach to decipher fluke molecular phenotypes independently of molecular parasite resistance mechanism(s), which are still not fully characterised or understood. Our findings confirmed the immunoreactivity and diagnostic potential of the present target antigens by sera from TCBZ-susceptible (TCBZ-S) and TCBZ-resistant (TCBZ-R) <i>F. hepatica</i> experimentally infected sheep.https://www.mdpi.com/1420-3049/25/15/3477fasciolosistriclabendazolediagnosticsbiomarkercalreticulintriose phosphate isomerase
spellingShingle Clare F. Collett
Russell M. Morphew
David Timson
Helen C. Phillips
Peter M. Brophy
Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics
Molecules
fasciolosis
triclabendazole
diagnostics
biomarker
calreticulin
triose phosphate isomerase
title Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics
title_full Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics
title_fullStr Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics
title_full_unstemmed Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics
title_short Pilot Evaluation of Two <i>Fasciola hepatica</i> Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics
title_sort pilot evaluation of two i fasciola hepatica i biomarkers for supporting triclabendazole tcbz efficacy diagnostics
topic fasciolosis
triclabendazole
diagnostics
biomarker
calreticulin
triose phosphate isomerase
url https://www.mdpi.com/1420-3049/25/15/3477
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