|M.Sc Student||Riahi Yael Ester|
|Subject||Characterization of New Targets for the Interruption of|
Differentiation and Pathogenesis of Entamoeba
|Department||Department of Medicine||Supervisor||Professor Serge Ankri|
Entamoeba histolytica is a protozoan parasite causing approximately 50 million cases of invasive colitis each year.
During bowel invasion, the parasite induces an inflammatory response that attracts neutrophils around invading amebas. Neutrophils fail to resist E.histolytica and they are rapidly killed by the parasite. The reasons for the inability of neutrophils to destroy the parasite are unknown. Activated neutrophils release cytotoxic molecules like cathepsin G. We have demonstrated that E.histolytica synthesizes a protein that belongs to the serine proteinase inhibitor (SERPIN) family. This serpin called Ehserp inhibits cathepsin G from human neutrophils. Ehserp is localized inside cytoplasmatic granules and is secreted only by amoeba co-incubated with mammalian cells. Ehserp inhibits cathepsin G by forming a tight complex resistant to detergent. This mechanism of inhibition is typical to the members of the inhibitory serpin family.
The ability of an Ehserp expressed in E.coli (rEhserp) to inhibit the activity of several serine proteinases was tested. Surprisingly rEhserp had a behavior of non-inhibitory serpin, being cleaved at it C-terminal part without forming a complex with cathepsin G. The secreted Ehserp has a size of 49 kDa whereas rEhserp has a size of 42 kDa. We have demonstrated that the difference of size and the difference of inhibitory activity are not associated with the presence of post-translational modifications like N -glycosylation, phosphorylation, or disulfide bonds, in the secreted serpin.
In conclusion, Ehserp is a powerful weapon used by the parasite to neutralize cathepsin G, a potent cytotoxic serine proteinase secreted by the neutrophils.