The sigma class glutathione transferase from the liver fluke Fasciola hepatica

Lacourse, E. James, 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, Arévalo, José Pérez, and Brophy, Peter M. (2012) The sigma class glutathione transferase from the liver fluke Fasciola hepatica. PLoS Neglected Tropical Disease, 6 (5). e1666. pp. 1-14.

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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 ID: 33415
Item Type: Article (Research - C1)
ISSN: 1935-2735
Additional Information:

© 2012 LaCourse et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: European Union (EU), BBSRC
Projects and Grants: EU DELIVER: Grant FOOD-CT-2005-023025, BBSRC grant BBH0092561, BBSRC grant BB/C503638/2
Date Deposited: 05 Jun 2014 03:33
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060109 Proteomics and Intermolecular Interactions (excl Medical Proteomics) @ 50%
07 AGRICULTURAL AND VETERINARY SCIENCES > 0707 Veterinary Sciences > 070708 Veterinary Parasitology @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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