Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica

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Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica. / Davis, Chelsea; Winters, Ana; Milic, Ivana; Devitt, Andrew; Cookson, Alan; Brophy, Peter; Morphew, Russ.

In: Scientific Reports, Vol. 10, 13445, 10.08.2020.

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@article{41eacf4f2a25424f96591b0b23fa1cab,
title = "Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica",
abstract = "Fascioliasis is a neglected zoonotic disease that infects humans and ruminant species worldwide. In the absence of vaccines, control of fascioliasis is primarily via anthelminthic treatment with triclabendazole (TCBZ). Parasitic flatworms, including Fasciola hepatica, are active secretors of extracellular vesicles (EVs), but research has not been undertaken investigating EV anthelmintic sequestration. Adult F. hepatica were cultured in lethal and sub-lethal doses of TCBZ and its active metabolites, in order to collect EVs and evaluate their morphological characteristics, production and anthelmintic metabolite content. Transmission electron microscopy demonstrated that F. hepatica exposed to TCBZ and its metabolites produced EVs of similar morphology, compared to non-TCBZ exposed controls, even though TCBZ dose and/or TCBZ metabolite led to measurable structural changes in the treated F. hepatica tegument. qNano particle analysis revealed that F. hepatica exposed to TCBZ and its metabolites produced at least five times greater EV concentrations than non-TCBZ controls. A combined mass spectrometry and qNano particle analysis confirmed the presence of TCBZ and the TCBZ–sulphoxide metabolite in anthelmintic exposed EVs, but limited TCBZ sulphone was detectable. This data suggests that EVs released from adult F. hepatica have a biological role in the sequestration of TCBZ and additional toxic xenobiotic metabolites.",
author = "Chelsea Davis and Ana Winters and Ivana Milic and Andrew Devitt and Alan Cookson and Peter Brophy and Russ Morphew",
year = "2020",
month = aug,
day = "10",
doi = "10.1038/s41598-020-69970-4",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Springer Nature",

}

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TY - JOUR

T1 - Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica

AU - Davis, Chelsea

AU - Winters, Ana

AU - Milic, Ivana

AU - Devitt, Andrew

AU - Cookson, Alan

AU - Brophy, Peter

AU - Morphew, Russ

PY - 2020/8/10

Y1 - 2020/8/10

N2 - Fascioliasis is a neglected zoonotic disease that infects humans and ruminant species worldwide. In the absence of vaccines, control of fascioliasis is primarily via anthelminthic treatment with triclabendazole (TCBZ). Parasitic flatworms, including Fasciola hepatica, are active secretors of extracellular vesicles (EVs), but research has not been undertaken investigating EV anthelmintic sequestration. Adult F. hepatica were cultured in lethal and sub-lethal doses of TCBZ and its active metabolites, in order to collect EVs and evaluate their morphological characteristics, production and anthelmintic metabolite content. Transmission electron microscopy demonstrated that F. hepatica exposed to TCBZ and its metabolites produced EVs of similar morphology, compared to non-TCBZ exposed controls, even though TCBZ dose and/or TCBZ metabolite led to measurable structural changes in the treated F. hepatica tegument. qNano particle analysis revealed that F. hepatica exposed to TCBZ and its metabolites produced at least five times greater EV concentrations than non-TCBZ controls. A combined mass spectrometry and qNano particle analysis confirmed the presence of TCBZ and the TCBZ–sulphoxide metabolite in anthelmintic exposed EVs, but limited TCBZ sulphone was detectable. This data suggests that EVs released from adult F. hepatica have a biological role in the sequestration of TCBZ and additional toxic xenobiotic metabolites.

AB - Fascioliasis is a neglected zoonotic disease that infects humans and ruminant species worldwide. In the absence of vaccines, control of fascioliasis is primarily via anthelminthic treatment with triclabendazole (TCBZ). Parasitic flatworms, including Fasciola hepatica, are active secretors of extracellular vesicles (EVs), but research has not been undertaken investigating EV anthelmintic sequestration. Adult F. hepatica were cultured in lethal and sub-lethal doses of TCBZ and its active metabolites, in order to collect EVs and evaluate their morphological characteristics, production and anthelmintic metabolite content. Transmission electron microscopy demonstrated that F. hepatica exposed to TCBZ and its metabolites produced EVs of similar morphology, compared to non-TCBZ exposed controls, even though TCBZ dose and/or TCBZ metabolite led to measurable structural changes in the treated F. hepatica tegument. qNano particle analysis revealed that F. hepatica exposed to TCBZ and its metabolites produced at least five times greater EV concentrations than non-TCBZ controls. A combined mass spectrometry and qNano particle analysis confirmed the presence of TCBZ and the TCBZ–sulphoxide metabolite in anthelmintic exposed EVs, but limited TCBZ sulphone was detectable. This data suggests that EVs released from adult F. hepatica have a biological role in the sequestration of TCBZ and additional toxic xenobiotic metabolites.

U2 - 10.1038/s41598-020-69970-4

DO - 10.1038/s41598-020-69970-4

M3 - Article

C2 - 32778698

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 13445

ER -

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