PATHWAYS REGULATING AMOEBIC CYST FORMATION

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DESCRIPTION: (Adapted from the Applicant'ps Abstract): Encystation in the human parasite Entamoeba histolytica cannot be studied in vitro. The related reptilian parasite, E. invadens, will encyst in vitro and can be used as model system to study encystation in Entamoeba. Two sugars inhibit the amebic encystation process. Galactose prevents the aggregation of ameba, which precedes encystation while N acetyl glucosamine allows aggregation to occur but still prevents the formation of osmotically resistant cysts. This proposal will study the role of galactose ligands and their receptor in the encystment process. An ortholog of the light subunit of the GalNAc lectin of E. histolytica has been cloned from E. invadens. The E. invadens gene product binds galactose and mucin, appears to be found on the surface of the ameba and likely mediates the initial cellular aggregation step. Gal-terminated glycoconjugates stimulate encystation in a concentration-dependent manner and suggest a role for the lectin in parasite differentiation. The structure of the lectin and a proposed mechanism of regulating encystation will be examined in this proposal.