Grant: Project Grant

Entamoeba histolytica (Eh) is a human parasite that is transmitted by direct ingestion of infective cysts in contaminated food or water. Eh infects ~10% of the world's population and causes the disease amebiasis (amoebic colitis and/or liver abscess) resulting in 100,000 deaths/year. This makes Eh the third leading cause of death by a parasite. It is a major global health problem especially in developing countries where children are mostly infected resulting in severe adverse health effects. The parasite colonizes and live in the protective mucus barrier in the colon by feeding on bacteria. To initiate disease, the parasite degrades the mucus barrier and kill intestinal cells by a process that is not well characterized. Our recent studies have unravelled that mucus contains structural proteins that build and stabilizes the mucus gel. This proposal examines the hypothesis that the parasite secrete enzymes that alter the protective nature of mucus by degrading mucus structural proteins to dissolve the mucus gel. This allows the parasite and bacterial to invade the gut that stimulates an acute inflammatory response that is tissue damaging to initiate intestinal disease. Using molecular biology tools and microscopic imaging techniques, we will determine how the parasite enzymes degrade mucus proteins to dissolve the mucus gel. This study will define the mechanism(s) on how disease is initiated in the mucus layer characteristic of most gastrointestinal pathogens, that can aid in the identification of novel strategies to combat infection.