Pathways regulating amoebic cyst formation

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DESCRIPTION (provided by the applicant): Entamoeba histolytica infects approximately 1% of the world's population, and causes up to 100,000 deaths annually. The disease-causing trophozoite stage of the parasite differentiates into the infectious cyst form while within the host colon, and the stimuli that induce this differentiation are only now becoming clear. We had previously found that galactose-terminated molecules, including those in colonic mucus, are used by the trophozoites to form cellular aggregates just prior to cyst formation. We have now found that short chain fatty acids, which are produced by the resident colonic bacterial population, can regulate the Entamoeba cyst formation process in a concentration-dependent manner. The effects of short chain fatty acids on the parasites are different from the effects these compounds have on other cells of the host, but they may be working through similar molecular mechanisms. This project will examine the mechanism(s) whereby these compounds regulate cyst formation, and will determine the extent of the effects these compounds have on gene and protein expression in the parasite.