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The Sigma Class Glutathione Transferase from the Liver Fluke Fasciola hepatica

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LaCourse, James ORCID: https://orcid.org/0000-0001-9261-7136, Perally, Samirah, Morphew, Russell M, Moxon, Joseph V, Prescott, Mark, Dowling, David J, O'Neill, Sandra M, Kipar, Anja, Hetzel, Udo, Hoey, Elizabeth, Zafra, Rafael, Buffoni, Leandro, Pérez Arévalo, José and Brophy, Peter M (2012) 'The Sigma Class Glutathione Transferase from the Liver Fluke Fasciola hepatica'. PLoS Neglected Tropical Diseases, Vol 6, Issue 5, e1666.

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Abstract

BACKGROUND

Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised.

METHODOLOGY/PRINCIPAL FINDINGS

In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection.

CONCLUSIONS/SIGNIFICANCE

We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity.

Item Type: Article
Subjects: QU Biochemistry > Enzymes > QU 141 Transferases
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
QX Parasitology > Helminths. Annelida > QX 365 Fasciola
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 950 Zoonoses (General)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pntd.0001666
Depositing User: Mary Creegan
Date Deposited: 21 Mar 2013 14:07
Last Modified: 06 Feb 2018 13:05
URI: https://archive.lstmed.ac.uk/id/eprint/3228

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