Dihydrofolate reductase and thymidylate synthetase in strains of Streptococcus faecium resistant to pyrimethamine, chlorguanide triazine, trimethoprim, and amethopterin

Abstract

Strains of Streptococcus faecium highly resistant to pyrimethamine, chlorguanide triazine or amethopterin exhibited increased levels of dihydrofolate reductase and thymidylate synthetase which varied from 2- to 40-fold. The increases in synthetase were always greater than the corresponding increases in reductase. A strain of the same organism resistant to trimethoprim, however, showed no increases in either enzyme. Studies on the partially purified reductases indicate that the pyrimethamine-resistant enzyme differs strikingly in certain molecular properties. This reductase had a pH optimum at about 5.0 whereas the other four enzymes showed optimum activity at about pH 6.O. It also showed altered inhibition profiles requiring from 4 times as much pyrimethamine to 40 times as much chlorguanide triazine as the sensitive enzyme to obtain 50% inhibition.