Authors

Discussion

The Liver flukes, Fasciola hepatica and F. gigantica are zoonotic parasitic flatworms of significant health and economic interest. Predictions on livestock production estimates losses at over $3 billion annually in reduction in meat, milk and other agriculturally significant yields. The WHO has also designated fascioliasis, liver fluke disease, as a neglected food borne human disease with up to 17 million infections and up to 200 million people living in areas at risk.  In absence of vaccines, the current mainstay treatment is Triclabendazole (TCBZ); the only drug effective against both juvenile and adult flukes. However, evidence of TCBZ resistance is now confirmed worldwide and new chemical compounds are being discovered or designed and synthesised to novel protein targets in liver flukes to combat increasing TCBZ resistance. Sigma class glutathione transferases (GSTs) aka prostaglandin D synthases offers a key target, due to well characterised role in immune modulation and limited relationship to host orthologues and potential roles in specific life cycle stages. Drug synthesis and testing has been performed using both recombinant and purified native enzyme extracts in order to validate this approach. Transcript analysis has uncovered another protein with suggested prostaglandin D synthase properties within F. hepatica proteome. Using various techniques this protein has been analysed structurally and functionally to determine the role played. Phylogenetic analysis of the GST clade across trematodes and free living helminths highlighted interesting factors in relation to extracellular vesicle content in their suggested role of host parasite interaction which requires further exploration.