Increased levels of dihydrofolate reductase in rifampin-resistant mutants of Bacillus subtilis.

Several independent, spontaneous rifampin-resistant mutants of Bacillus subtilis were isolated and found to have an increased resistance to trimethoprim, an inhibitor of dihydrofolate reductase. This increased resistance in the rif mutants was the result of a specific threefold increase in the activity of dihydrofolate reductase, since six other enzymes examined remained unchanged. This increased level of dihydrofolate reductase and the trimethoprim resistance were cotransformed (100%) with the rif marker. These results suggest that the RNA polymerase is altered in its recognition of the gene that specifies dihydrofolate reductase.