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.