How do sulfonamides exert their antibacterial effect?

• A. RNA polymerase inhibition
• B. Inhibition of dihydropteroate synthase in folate synthesis, reducing nucleotide production
• C. Disruption of the cell membrane
• D. Inhibition of protein synthesis at the 70S ribosome

Answer: (B)

Sulfonamides work by mimicking PABA, the normal substrate for dihydropteroate synthase in bacterial folate synthesis. They competitively inhibit this enzyme, blocking the formation of dihydropteroate and, subsequently, tetrahydrofolate. Without tetrahydrofolate, the bacteria can’t efficiently synthesize nucleotides needed for DNA and RNA, halting growth. Humans don’t synthesize folate and obtain it from diet, giving selective toxicity to these drugs. The other mechanisms listed—affecting RNA polymerase, disrupting the cell membrane, or inhibiting 70S ribosomal protein synthesis—are not how sulfonamides exert their effect.