Which statement correctly identifies a mechanism of action for sulfonamides?

• A. They inhibit Dihydrofolate Reductase
• B. They inhibit Dihydropteroate Synthase
• C. They inhibit 30S Ribosomal Subunit
• D. They disrupt DNA Gyrase

Answer: (B)

Sulfonamides work by blocking a step in bacterial folate synthesis. They act as competitive inhibitors of dihydropteroate synthase, the enzyme that uses PABA to make dihydropteroate, a precursor to dihydrofolate and then tetrahydrofolate. Without tetrahydrofolate, bacteria can’t synthesize thymidylate and purines needed for DNA replication and repair, so growth is halted in actively dividing cells. Humans don’t synthesize folate and instead obtain it from the diet, so our cells aren’t as affected, which explains the selective toxicity of these drugs.

Other mechanisms mentioned correspond to different antibiotic classes: inhibiting dihydrofolate reductase is the action of trimethoprim; inhibiting the 30S ribosomal subunit targets protein synthesis (as with certain aminoglycosides and tetracyclines); disrupting DNA gyrase is what fluoroquinolones do.