Plasmodium falciparum: variations in p-aminobenzoic acid requirements as related to sulfadoxine sensitivity

Plasmodium falciparum, Thai strain FCM-5S sensitive to sulfadoxine, was grown continuously for 1 year in a medium with a low concentration of p-aminobenzoic acid (PABA) without the emergence of a sulfadoxine-resistant line. The minimum PABA-requirement for growth of sulfadoxine-sensitive Thai strains in vitro was found to be 25.0 ng/ml, whereas resistant Burmese and Gambian strains completed their schizogony in the absence of PABA. Cultivation in dialyzed and nondialyzed human serum suggested that the sulfadoxine-resistant parasite might use another serum factor in place of PABA for folate biosynthesis, thus overcoming the effect of sulfadoxine, a PABA antagonist. The significantly lower rate of [14C]sulfadoxine incorporation into erythrocytes infected with sulfadoxine-resistant strains strongly supports this suggestion.