Sulfamethoxazole and trimethoprim work synergistically to inhibit bacterial growth. Sulfamethoxazole blocks dihydropteroate synthetase, an enzyme vital for folic acid synthesis. This enzyme is absent in mammals, resulting in selective toxicity.
Trimethoprim inhibits dihydrofolate reductase, another enzyme in the folic acid pathway. This enzyme is present in both bacteria and mammals, but trimethoprim binds to the bacterial enzyme with much higher affinity, further enhancing the antibacterial effect.
The combined action significantly reduces the minimum inhibitory concentration (MIC) needed to stop bacterial growth compared to either drug alone. This synergistic effect accounts for the drug’s broad-spectrum activity against many Gram-positive and Gram-negative bacteria.
| Sulfamethoxazole | Dihydropteroate synthetase | Inhibits folic acid synthesis |
| Trimethoprim | Dihydrofolate reductase | Inhibits folic acid metabolism |
Specifically, this disruption of folic acid metabolism prevents the synthesis of purines and pyrimidines, essential building blocks of bacterial DNA and RNA. This ultimately halts bacterial reproduction and leads to bacterial death. This sequential blocking of the folic acid pathway makes resistance development less likely than with single-agent therapy.
