Glycogen Metabolism and Its Role in Growth and Encystation in Entamoeba histolytica

Entamoeba histolytica is a parasitic protozoan that causes diarrheal disease in approximately 100 million people worldwide every year. E. histolytica has two forms, the growing trophozoite and the infectious cyst. Trophozoites colonizing the large intestine form cysts that are released into the environment. The ingestion of the cysts in contaminated food and water continues the disease cycle. Here, we investigated the role of glycogen in trophozoite growth and encystation. Glycogen is thought to provide precursors for the synthesis of chitin, a major component of the protective cyst wall. We propose that glycogen also serves as an energy source during metabolic adaptation to different nutrient environments. We examined the role of glycogen in E. histolytica by analyzing the growth and encystation of RNAi strains with reduced expression of the single gene-encoding glycogen synthase (GYS) or two of three genes encoding glycogen phosphorylase (PYG). The GYS RNAi strain had a greatly reduced glycogen accumulation, and both the GYS and PYG RNAi strains exhibited reduced growth in the glucose-poor medium. Both RNAi strains also showed reduced cyst production. Our results suggest glycogen synthesis and degradation are vital to the growth and adaptation of E. histolytica to a low-glucose environment such as that encountered in the large intestine.