Aminoglycoside resistance via aminoglycoside-modifying enzymes (AMEs) is the most common mechanism globally. The three types of AMEs that modify aminoglycosides are acetyltransferases, phosphotransferases, and nucleotidyltransferases. They share the common consequence of:

• A Increasing the drug's polarity, impairing transport through the inner membrane EDP-II system
• B Converting aminoglycosides to derivatives that bind efflux pump substrates and are actively exported
• C Methylating the 16S rRNA at position m7G1405 directly rather than modifying the drug molecule
• D Reducing the drug's affinity for the 16S rRNA A-site by steric hindrance of ribosomal binding ✓

Explanation

Aminoglycoside-modifying enzymes (acetyltransferases-AAC, phosphotransferases-APH, nucleotidyltransferases-ANT) chemically modify the aminoglycoside at specific hydroxyl or amino groups. These modifications reduce the drug's affinity for its ribosomal target—the 16S rRNA at the decoding A-site. The modified aminoglycoside cannot bind the ribosome effectively and bactericidal activity is lost. Methylation of 16S rRNA (e.g., by RmtA-RmtH methyltransferases) is a separate high-level pan-aminoglycoside resistance mechanism that modifies the target rather than the drug. Efflux and impaired transport are lesser mechanisms.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.