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The intestinal parasite Entamoeba histolytica (Eh) is a significant health risk in the developing world where infection occurs via ingestion of contaminated food or water. The resulting disease, amebiasis, claims 100,000 lives each year. In the colon, the parasite colonizes the mucous layer and interacts with the underlying mucosa to induce a variety of symptoms. The intestinal barrier has three main components: bacteria and host proteins found within the lumen, a protective layer of mucus, and a single layer of intestinal epithelial cells (IEC) connected by tight junctions (TJ). Eh possesses a variety of virulence components that target the intestinal barrier to cause increased gut permeability, resulting in diarrhea. In the colon Eh can phagocytose pathogenic bacteria, which may increase the virulence of the parasite. Moreover, Eh binds colonic mucins via the parasite surface Gal/GalNAc lectin to facilitate colonization of the mucous layer. Subsequently, the virulence factor, EhCP-A5, degrades the MUC2 polymer, allowing the parasite access to the epithelia where it binds to and destroys IEC by apoptosis or alters the expression of TJ proteins, causing secretory diarrhea. The sequence of events in intestinal amebiasis is not well understood and is based largely on in vitro and in vivo models of the disease. |
