Dihydropteroate synthase polymorphisms in Pneumocystis carinii

Sulfa drugs are widely used in the treatment and prophylaxis of Pneumocystis carinii pneumonia. The nucleotide sequences of the sulfa target enzyme, dihydropteroate synthase (DHPS), differed substantially in human-, rat-, and mouse-derived P. carinii. Sequence variation also existed in the DHPSs from human-derived isolates. Six nucleotide changes were found in 6 human isolates; each was nonsynonymous and resulted in an amino acid change. Several of these changes were in highly conserved regions and are similar to those that cause sulfa resistance in other organisms. These data suggest that the human-derived P. carinii DHPS may be evolving under positive selective pressure from sulfa drugs.