Cysteine proteinases and the pathogenesis of amebiasis

Amebiasis is a major cause of morbidity and mortality throughout the tropic al world. Entamoeba histolytica is now recognized as a separate species fro m the morphologically identical E. dispar, which cannot invade. Cysteine pr oteinases are a key virulence factor of E. histolytica and play a role in i ntestinal invasion by degrading the extracellular matrix and circumventing the host immune response through cleavage of secretory immunoglobulin A (sI gA), IgG, and activation of complement. Cysteine proteinases are encoded by at feast seven genes, several of which ave found in E. histolytica but not E. dispar. A number of new animal models, including the formation of liver abscesses in SCID mice and intestinal infection in human intestinal xenogr afts, have proven useful to confirm the critical role of cysteine proteinas es in invasion. Detailed structural analysis of cysteine proteinases should provide further insights into their biochemical function and may facilitat e the design of specific inhibitors which could be used as potential chemot herapeutic agents in the future.