What is the mechanism of action of sulfonamides?

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Multiple Choice

What is the mechanism of action of sulfonamides?

Sulfonamides work by blocking bacterial folate synthesis. They are structural cousins of PABA and competitively inhibit the enzyme dihydropteroate synthase, preventing the combination of PABA with para-aminobenzoic acid to form dihydropteroate. This stops the production of dihydrofolic acid and ultimately tetrahydrofolate, a cofactor needed to make nucleotides for DNA and RNA. Without tetrahydrofolate, bacteria can’t synthesize thymidine and purines, so growth is halted. Humans aren’t affected in the same way because we obtain folate from our diet and don’t synthesize it de novo, giving selective toxicity to the drug. When used with trimethoprim, which blocks a later step (dihydrofolate reductase), the blockade of folate metabolism is even more complete, enhancing the antibacterial effect. The other mechanisms described correspond to different antibiotic classes (protein synthesis inhibitors, cell wall synthesis inhibitors, or DNA synthesis inhibitors) and are not how sulfonamides work.

Sulfonamides work by blocking bacterial folate synthesis. They are structural cousins of PABA and competitively inhibit the enzyme dihydropteroate synthase, preventing the combination of PABA with para-aminobenzoic acid to form dihydropteroate. This stops the production of dihydrofolic acid and ultimately tetrahydrofolate, a cofactor needed to make nucleotides for DNA and RNA. Without tetrahydrofolate, bacteria can’t synthesize thymidine and purines, so growth is halted. Humans aren’t affected in the same way because we obtain folate from our diet and don’t synthesize it de novo, giving selective toxicity to the drug. When used with trimethoprim, which blocks a later step (dihydrofolate reductase), the blockade of folate metabolism is even more complete, enhancing the antibacterial effect. The other mechanisms described correspond to different antibiotic classes (protein synthesis inhibitors, cell wall synthesis inhibitors, or DNA synthesis inhibitors) and are not how sulfonamides work.

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