Amino acid supplementation confers protection to red blood cells before Plasmodium falciparum bystander stress

Malaria is a highly oxidative parasitic disease in which anemia is the most common clinical symptom. A major contributor to the malarial anemia pathogenesis is the destruction of bystander, uninfected red blood cells (RBCs). Metabolic fluctuations are known to occur in the plasma of individuals with acute malaria, emphasizing the role of metabolic changes in disease progression and severity. Here, we report conditioned medium from Plasmodium falciparum culture induces oxidative stress in uninfected, catalase-depleted RBCs. As cell-permeable precursors to glutathione, we demonstrate the benefit of pre-exposure to exogenous glutamine, cysteine, and glycine amino acids for RBCs. Importantly, this pretreatment intrinsically prepares RBCs to mitigate oxidative stress.