Grant: Project Grant

Entamoeba histolytica is a parasite that cause the disease amebiasis, which results in 100,000 deaths/year. The parasite colonizes and live in mucus and feeds on bacteria. To initiate disease, the parasite has to overcome the protective mucus barrier to invade intestinal cells that is not well characterized. Our recent studies have shown that mucus contains structural proteins that build and stabilize the mucus gel. This proposal examines the hypothesis that E. histolytica secreted enzymes degrade a major mucus associated protein allowing the parasite to gain access and cleave MUC2 mucin to abrogate mucus protective functions. This allows the parasite to gain access to underlying colonic epithelial cells in the gut that trigger inflammation and tissue invasion. To study this, we will use biochemical techniques to characterize how the mucus proteins interact and by microscopic imaging techniques we will quantify how the parasite enzymes degrade mucus structural components. This study will define the mechanism on how disease is initiated by E. histolytica to dissolve the mucus layer, which can aid in the identification and development of novel strategies to combat infection.