Aminoglycosides achieve their bactericidal effect against aerobic Gram-negative bacilli through a specific sequence. The INITIAL step in their mechanism of action is:
- A Irreversible binding to the 50S ribosomal subunit causing premature chain termination
- B Disruption of the outer membrane lipopolysaccharide via displacement of divalent cations
- C Energy-dependent uptake across the bacterial inner membrane, facilitated by the transmembrane electrical potential ✓
- D Binding to the 30S ribosomal subunit prevents initiator tRNA from aligning at the P site
Explanation
Aminoglycosides (gentamicin, amikacin, tobramycin) enter bacteria in a stepwise process. After initial ionic binding to LPS on the outer membrane, the first step of intracellular entry (Phase I uptake) is an energy-dependent process driven by the electrochemical gradient (proton motive force) across the inner membrane. This phase is inhibited by anaerobic conditions, low pH, and hyperosmolarity—explaining why aminoglycosides are inactive against strict anaerobes and in abscess cavities. Once inside, they bind the 30S subunit (specifically 16S rRNA at the A site) and cause misreading of mRNA, producing aberrant proteins that insert into the cell membrane and initiate a feedback loop increasing permeability and further aminoglycoside uptake.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.