Entamoeba histolytica is a water- and food-borne intestinal parasite that causes diarrheal disease in an estimated 90 million people each year worldwide. This pathogen encounters many different environments during infection and must adjust its metabolic activities specifically to that environment. Entamoeba lacks many common metabolic pathways and must ingest other cells to obtain many of the cellular building blocks such as amino acids that it cannot synthesize itself. E. histolytica relies on breakdown of the sugar glucose as the main means for obtaining energy. This is done through glycolysis, a metabolic pathway that is present in essentially all organisms. A key enzyme in glycolysis is phosphofructokinase (PFK). E. histolytica has four PFKs: PFK4 is thought to be the primary enzyme in glycolysis but the roles of PFK1, PFK2, and PFK3 are as yet unknown. PFK4 utilizes pyrophosphate, which increases the energy output of glucose breakdown by glycolysis; however, PFKs1-3 all use ATP, the main energy currency in the cell. In order to understand the role of the ATP-PFKs, we are silencing the genes encoding them and determining the effect on cell growth on glucose and other substrates. We are also characterizing the activity and regulation of purified PFK1, PFK2, and PFK3. Currently, the model systems for infection of E.histolytica are not quite advanced and an animal model that mimics human infection is lacking. Thus, no one has been achieved a full understanding of metabolism during the different stages of infection. Our studies will contribute to a better understanding of energy metabolism in E. histolytica and will fill a gap in our knowledge of how this parasite survives and thrives in the different environments encountered during infection in humans leading to symptomatic disease.
Bastuzel, Irem and Ingram-Smith, Cheryl, "Metabolic adaptation during infection in the intestinal parasite Entamoeba histolytica: roles of PFK enzymes" (2019). Graduate Research and Discovery Symposium (GRADS). 240.