Project Details

Establishing the role of erythrocyte glycolysis in the Plasmodium falciparum lifecycle

Sesh Sundararaman, MD, PhD

Summary

BACKGROUND: The malaria parasite, Plasmodium falciparum, causes millions of infections and over five hundred thousand deaths per year, predominantly in young children. Antimalarial drug resistance is increasing and novel therapies are urgently needed to combat this global threat. GAP: P. falciparum infects host red blood cells during the intraerythrocytic lifecycle. While red blood cells are essential to the parasite lifecycle, we do not understand which red blood cell pathways are needed and why. Understanding why red blood cell pathways are required by the parasite could lead to the development of new red blood cell directed antimalarial drugs. HYPOTHESIS: Studies have shown that inhibiting red blood cell glycolysis decreases P. falciparum growth. I hypothesize that inhibiting red blood cell glycolysis perturbs redox balance in infected cells, increasing the parasite’s susceptibility to oxidative stress. METHODS: Using well characterized inhibitors, I will block red blood cell glycolysis and examine the effects on parasite glycolysis, growth, redox balance, and susceptibility to oxidative stress. I will then examine if the parasite can adapt to partial inhibition of red blood cell glycolysis. RESULTS: Pending. IMPACT: This study will establish the role of red blood cell glycolysis in the P. falciparum lifecycle. My findings will guide future antimalarial drug development and determine if glycolytic inhibitors that are currently being developed for cancer therapy can be repurposed as antimalarial drugs.