Authors

Discussion

Schistosomiasis causes 280,000 deaths per year in sub-Saharan Africa exclusively. Subsequently, the World Health Organisation (WHO) reported that 206 million people required treatment for schistosomiasis in 2016.Globally, a third of all infections are due to Schistosoma mansoni. At present, control is heavily focused on the administration of anthelmintics, an approach not regarded as sustainable. Thus, research is targeted towards the development of novel vaccines including those based on recombinant proteins. The glutathione transferase (GST) protein family has long been identified as a source of such vaccine candidates to eradicate schistosomiasis. However, the mechanism of action is poorly understood and the complete understanding of the GST family itself is lacking. Thus, vaccine trials incorporating GST components have stalled. The aim of the current study was to utilise high resolution proteomics technology supported by in depth bioinformatics, to explore the full capacity of the GST family in S. mansoni. Bioinformatic characterisation of the S. mansoni genome revealed 3 classes of GST (Mu, Microsomal, and Omega) with multiple members within the Mu class. Following GST affinity purification, using glutathione agarose, high resolution proteomics in combination with Western blotting has confirmed the presence of both sigma and mu class GSTs in the adult soma. In addition, we have explored GST expression associated with extracellular vesicles (EVs). EVs were purified from adult excretory/secretory products using size exclusion chromatography. Transmission electron microscopy with target GST gold labelling has been established to investigate sigma class GST expression on the surface of S. mansoni EVs. This study has deepened our understanding of the GST family in S. mansoni and will assist the development of an improved schistosomiasis vaccine based on GST.