The structure, function and expression of the Gal/GalNac lectin and virulence proteins of Entamoeba histolytica

Entamoeba histolytica colonizes the intestinal tract of humans, causing amebic colitis in 10% of infected patients, and persists in the host for months. The mechanism of persistence is unknown. Colonization and adherence to the host is mediated by the galactose/N-acetyl/-D-galactosamine (Gal/GalNAc)-specific lectin. Antibodies to the carbohydrate recognition domain of the Gal/GalNAc lectin heavy subunit mediate protection against reinfection. It has recently been observed that E. histolytica clinical isolates show tremendous diversity at the serine-rich E. histolytica protein (SREHP) locus. We have determined that unlike the SREHP locus, the Gal/GalNAc lectin shows considerable sequence conservation among clinical isolates. We have confirmed that the Gal/GalNAc lectin is captured by host cells in vitro, and expanded these finding by showing that it is captured by host cells in vivo. We describe and characterize the expression of an unusually large family of transmembrane kinases that have homology to the Gal/GalNAc lectin. We show that the transmembrane kinase superfamily consists of six subfamilies of transmembrane kinases, and that some members of each of these families are expressed in vitro . Additionally, we describe a large family of leucine-rich-repeat containing proteins. Finally, we have constructed an oligoarray and characterized the in vitro expression profile of these genes, setting the stage for an in vivo analysis of gene expression. We conclude that E. histolytica expresses a complex set of membrane and secreted virulence determinants. The presence of multiple receptor kinases in the plasma membrane offers for the first time a potential explanation of the ability of the parasite to respond to the changing environment of the host.