Identification of E. histolytica virulence factors

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DESCRIPTION (provided by applicant): Diarrheal diseases kill one of every ten children by his or her fifth birthday in poor countries such as Bangladesh. Entamoeba histolytica is one of the etiologic agents. It is a human parasite that has a remarkable ability to invade and lyse host tissues. Invasive infection with E. histolytica leads to dysentery, amebic colitis, and amebic liver abscess. The imminent completion of the Entamoeba genome project provides an unprecendented opportunity to apply the approaches of genetics to the problem of amebiasis. Three specific aims are proposed: (1) Characterize the host:parasite interface by identifying molecules recruited to this site by the E. histolytica GalNAc lectin using a yeast two-hybrid system, (2) Use a proteomics approach in conjunction with the E. histolytica genome sequencing database to further characterize novel proteins that interact with the GalNAc lectin, and (3) Investigate the biological significance of E. histolytica proteins recruited by the GalNAc lectin to the host:parasite interface by creating "knockout" mutants of these proteins using interference RNA (RNAi), antisense RNA technology, and/or expression of dominant negative mutants. Successful completion of these studies will yield a fundamental understanding of amebic proteins that interact with the E. histolytica GalNAc lectin and their role in pathogenicity.