Tetracyclines inhibit bacterial protein synthesis. The primary mechanism of resistance in clinical gram-negative isolates involves which process?

• A Target site mutation — ribosomal 30S subunit mutation at the tetracycline binding site
• B Enzymatic inactivation — tetracycline-inactivating monooxygenases encoded on resistance plasmids
• C Reduced outer membrane permeability — loss of OmpF porins exclusively in gram-negative organisms
• D Active efflux — Tet efflux pumps encoded by tet genes (e.g., tetA, tetB) export tetracyclines from the bacterial cytoplasm via proton-antiport mechanism ✓

Explanation

The predominant mechanism of tetracycline resistance in clinical gram-negative bacteria is active efflux mediated by Tet efflux proteins (TetA, TetB, TetC etc.) encoded on mobile resistance plasmids. These are members of the major facilitator superfamily (MFS) that use the proton electrochemical gradient as an energy source to export tetracycline-Mg2+ chelate complexes out of the bacterial cytoplasm. TetA is the most common in enterobacteriaceae. Importantly, tigecycline (a glycylcycline) and omadacycline (an aminomethylcycline) are poor substrates for these Tet efflux pumps and ribosomal protection proteins, explaining their activity against tetracycline-resistant organisms. Target site mutations and enzymatic inactivation are less common 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.