Back to Search
Start Over
The Sigma class glutathione transferase from the liver fluke Fasciola hepatica.
- Source :
-
PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2012; Vol. 6 (5), pp. e1666. Date of Electronic Publication: 2012 May 29. - Publication Year :
- 2012
-
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.<br />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.<br />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.
- Subjects :
- Animals
Antigens, Helminth genetics
Antigens, Helminth immunology
Antigens, Helminth metabolism
Blotting, Western
Disease Models, Animal
Fasciola hepatica immunology
Fascioliasis immunology
Fascioliasis pathology
Gene Expression Profiling
Glutathione Transferase immunology
Goats
Immunohistochemistry
Mice
Mice, Inbred C57BL
Parasite Load
Prostaglandin-Endoperoxide Synthases genetics
Prostaglandin-Endoperoxide Synthases immunology
Prostaglandin-Endoperoxide Synthases metabolism
Recombinant Proteins genetics
Recombinant Proteins immunology
Recombinant Proteins metabolism
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic immunology
Fasciola hepatica enzymology
Fascioliasis prevention & control
Glutathione Transferase genetics
Glutathione Transferase metabolism
Vaccination methods
Subjects
Details
- Language :
- English
- ISSN :
- 1935-2735
- Volume :
- 6
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PLoS neglected tropical diseases
- Publication Type :
- Academic Journal
- Accession number :
- 22666515
- Full Text :
- https://doi.org/10.1371/journal.pntd.0001666