Co-trimoxazole Mechanism of action
Tetrahydrofolic acid is essential for the bacteria to produce one-carbon units which are required for DNA and protein synthesis. If tetrahydrofolic is not formed, growth will slow. Sulfamethoxazole,a member of the sulfonamide group, competitively inhibits para-aminobenzoic incorporation intodihydrofolic acid (Step 1, and see earlier lecture for details and for explanation of selective toxicity). Trimethoprim inhibits dihydrofolic acid reductase (Step 2), thus inhibiting tetrahydrofolic acid formation. The reason for the selective toxicity of trimethoprim is that it is much more inhibitory tothe bacterial than to the human enzyme. Thus, by inhibiting sequential steps in the metabolicpathway, a synergistic antibacterial effect is produced.