Aminoglycoside resistance mediated by aminoglycoside-modifying enzymes (AMEs) is clinically the most important resistance mechanism. Which enzyme class causes resistance specifically by preventing drug binding to the 30S ribosomal subunit target?

• A Aminoglycoside acetyltransferases (AACs), phosphotransferases (APHs), and nucleotidyltransferases (ANTs) — all modify aminoglycosides' hydroxyl or amino groups, reducing electrostatic affinity for 16S rRNA
• B Efflux pumps of the MexXY-OprM type — actively pump aminoglycosides out of Pseudomonas cells
• C 16S rRNA methyltransferases (armA, rmtB) — methylate the rRNA target site itself, conferring very high-level pan-aminoglycoside resistance ✓
• D Outer membrane porin (OprD) loss — reduces aminoglycoside entry into gram-negative cells

Explanation

While AMEs (AACs, APHs, ANTs) are the most common mechanism quantitatively, 16S rRNA methyltransferases (encoded by genes like armA, rmtA-H, npmA) confer the highest level of resistance by methylating specific adenine residues in the 16S rRNA drug-binding site, directly preventing aminoglycoside binding. This mechanism confers resistance to all aminoglycosides simultaneously (pan-aminoglycoside resistance) with MICs >256 mg/L. AMEs modify the drug itself (not the target), reducing affinity. The question asks specifically which class prevents drug binding to the target, making 16S rRNA methyltransferases the most precise answer.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.