What is the mechanism of action of aminoglycoside antibiotics on bacteria?

• A. Inhibit cell wall synthesis
• B. Inhibit DNA replication
• C. Irreversibly bind to the 30S ribosomal subunit causing misreading of mRNA and defective protein synthesis
• D. Block folic acid synthesis

Answer: (C)

Aminoglycosides kill bacteria by binding irreversibly to the 30S subunit of the bacterial ribosome. This interaction disrupts the initiation complex and impairs the proofreading function during translation, causing the ribosome to read mRNA incorrectly. The result is incorporation of incorrect amino acids and the production of defective, often toxic, proteins. The buildup of faulty proteins damages the cell and contributes to bactericidal activity.

Uptake of aminoglycosides into bacteria requires active transport that depends on the proton motive force and oxygen; therefore these drugs are most effective against aerobic, Gram-negative organisms and less active in anaerobic environments.

These antibiotics do not block cell wall synthesis (that’s the realm of beta-lactams and glycopeptides), do not inhibit DNA replication (quinolones do), and do not block folic acid synthesis (sulfonamides and trimethoprim do). In practice, they may be used with a beta-lactam to enhance bacterial killing by improving drug entry through damaged cell walls.