Effect of dietary p-aminobenzoic acid on murine Plasmodium yoelii infection.

Plasmodia species, unlike humans, can utilize p-aminobenzoic acid (PABA) for the de novo generation of folate. Plasmodial enzymes for the synthesis of PABA via the shikimate pathway are being investigated as novel targets for malaria chemotherapy. We show that, despite the presence of biosynthetic machinery to synthesize PABA, Plasmodium yoelii, a rodent malaria species, requires exogenous dietary PABA for survival. Mice fed low-PABA diets do not die from lethal doses of P. yoelii. The initiation of a PABA-deficient diet after P. yoelii infection is established leads to the clearance of parasites and subsequent resistance to infection by P. yoelii. An intact immune system is not necessary for protection, given that mice with severe combined immunodeficiency were also protected by PABA-deficient diet. Our studies suggest that the PABA content in the diet will affect the host clearance of malaria parasites and may affect the efficacy of treatments that target the shikimate pathway.