DIHYDROPTEROATE SYNTHASE POLYMORPHISMS IN PNEUMOCYSTIS-CARINII

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