Authors

Discussion

Cystatins are a superfamily of tight-binding reversible inhibitors of papain like cysteine proteases and are found in a variety of organisms. Given the abundance and various functions of cysteine proteases secreted by the parasitic trematode Fasciola hepatica such as nutrition, infection and protection, their regulation by cysteine protease inhibitors is of utmost importance as the regulation of proteolytic activity is a crucial protective process within Fasciola.Based on recent genome and associated stage specific analysis, we have identified several genes encoding cystatins.  We have successfully expressed a family of three active F.hepatica cystatins in Pichia pastoris, achieving a high purified yield. Extensive biochemical characterisation revealed each of these cystatins to be broad and potent inhibitors of F. hepatica cathepsin L and B, as well as human cathepsins L, K, B and S. Inhibition of these cysteine proteases and their stage-specific expression suggests a role for F. hepatica cystatins in the regulation of parasite processes including penetration, feeding, development and immune evasion, as well as antigen processing & presentation by the host, which can be exploited for vaccine development.