The Sigma Class Glutathione Transferase from the Liver Fluke Fasciola hepatica

Abstract

BackgroundLiver 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 FindingsIn 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/SignificanceWe 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.

Auranofin-induced oxidative stress causes redistribution of the glutathione pool in Taenia crassiceps cysticerci

“…The first defensive line of these parasites is represent by glutathione peroxidase (GPx) [57][58][59] and peroxiredoxins (Prx) [60][61][62][63][64], which acts as ROS scavengers, as well as glutathione S-transferase (GST) [65][66][67], involved in the elimination of xenobiotic compounds. Both of these protective systems are dependent of the glutathione-reductase activity of the multifunctional TGR.…”

Generating a detailed protein profile of Fasciola hepatica during the chronic stage of infection in cattle

“…The immunomodulation capabilities of the liver fluke has been well described . The observation that prostaglandin E synthase 3 in only the SPF fraction indicates that the tegumental part of the parasite may play a specific role in this immunomodulation process.…”

Transcriptome profiling of the fifth-stage larvae of Angiostrongylus cantonensis by next-generation sequencing

“…GST in Fasciola hepatica influences host immune cell activities. It is present near the surface of the fluke and is expressed in eggs and newly excysted larvae as well as in the excretory/secretory fraction of the adults (LaCourse et al 2012). In Opisthorchis viverrini , GST is one of the excretory/secretory products (ESP) and acts as a mitogen.…”