Antibacterial synergism: a proposal for chemotherapeutic potentiation between trimethoprim and sulfamethoxazole.

Sulfamethoxazole and other sulfa drugs are moderately potent inhibitors of Escherichia coli dihydrofolate reductase. They also significantly potentiate the inhibition of this enzyme by trimethoprim. The molecular basis for inhibition potentiation is the simultaneous binding of trimethoprim and sulfa by the enzyme. This potentiation may explain the synergism observed when these drugs are used in antibacterial chemotherapy.