Characterization of different plasmid-borne dihydropteroate synthases mediating bacterial resistance to sulfonamides.

Plasmid-borne resistance to sulfonamides was studied in both newly isolated and earlier characterized R plasmids. Two different classes of drug-resistant dihydropteroate synthases were found to be responsible for most cases of plasmid-mediated sulfonamide resistance. The plasmid-coded enzymes could be completely separated from their chromosomal counterpart and also showed differences in heat stability and molecular size. The resistant and chromosomal enzymes could bind the normal substrate, p-aminobenzoic acid, with equal efficiency. In contrast, sulfonamide binding was about 10,000 times lower with the plasmid-coded enzymes than with the chromosomal enzyme. Another substrate analog, p-aminosalicylic acid, on the other hand, inhibited chromosomal and plasmid-mediated enzymes to a similar extent. Evidence was also found for the existence of a plasmid-borne resistance mechanism independent of drug-insensitive enzymes.