What general mechanism do macrolides use to inhibit bacterial growth?

• A. They bind to the 50S ribosomal subunit, blocking translocation during protein synthesis.
• B. They bind to the 30S ribosomal subunit causing misreading of mRNA.
• C. They inhibit DNA gyrase and topoisomerase IV.
• D. They inhibit dihydropteroate synthase in folate synthesis.

Answer: (A)

Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking translocation during elongation. This binding, at the 23S rRNA portion of 50S near the peptidyl transferase center, prevents the ribosome from moving along the mRNA, causing the growing polypeptide to stall and stopping protein production. That interruption of elongation is why macrolides are typically bacteriostatic. Other drug classes act on different targets: binding to the 30S subunit causing misreading of mRNA is characteristic of aminoglycosides; inhibiting DNA gyrase and topoisomerase IV is how fluoroquinolones work; and inhibiting dihydropteroate synthase in folate synthesis is the mechanism of sulfonamides.