Grant: Operating Grant

The parasite Entamoeba histolytica causes the disease amebiasis, which results in 100,000 deaths/year. How the parasite cause disease is not known but it has to overcome the protective mucus barrier to invade intestinal cells. The parasite attaches to colonic mucins (proteins in mucus) and the gut lining via a surface protein prior to causing disease. This proposal examines the hypothesis that E. histolytica secreted cysteine proteinases (enzymes) and prostaglandin (PGE2, an inflammatory mediator) play major roles in altering the protective mucus barrier in the pathogenesis of intestinal amebiasis. The study will characterize how the enzymes released by the parasite break down the protective mucus proteins and dissolve the mucus barrier. In addition, the parasite also produces PGE2 that not only cause depletion of mucus but also stimulate inflammation in the gut which help the parasite to cause disease. We are proposing to study how cysteine proteinase and PGE2 together can synergize to help the parasite cause disease. By studying both these virulent factors, the results of this study will define the mechanisms of how disease is initiated by this parasite and in the identification of novel strategies to control this medically important pathogen.