Dihydrofolate Reductases in Some Folate-Requiring Bacteria with Low Trimethoprim Susceptibility

Abstract

Dihydrofolate reductases from the folate-requiring strains Streptococcus faecalis ATCC 8043, Lactobacillus casei ATCC 7496, and Pediococcus cerevisiae ATCC 8081, as well as from Lactobacillus arabinosus , which is not dependent on exogenous folate, were isolated, and their properties were compared to reductases of Escherichia coli B, Staphylococcus aureus , and rat liver reductase. An inhibition profile with six different inhibitors revealed significant differences among all enzymes. All lactobacilli reductases are less sensitive to trimethoprim than the enzymes of E. coli and S. aureus , the reductase of P. cerevisiae requiring a concentration at least 1,000 times higher for 50% inhibition. Inhibition of growth of S. faecalis by pyrimethamine and 2,4-diamino-6,7-diisopropyl-pteridine was seen to be much stronger than was predicted from the enzymatic data.