Tigecycline, a glycylcycline, overcomes tetracycline resistance via which mechanism compared to earlier tetracyclines?

• A Tigecycline inhibits DNA gyrase in addition to ribosomal 30S subunit binding
• B Tigecycline has a unique 70S ribosome binding site different from classical tetracycline binding
• C Tigecycline is activated intracellularly by bacterial nitroreductases
• D Tigecycline is not a substrate for the Tet(A-E) efflux pumps and Tet(M) ribosomal protection proteins — the bulky C-9 glycylamido substituent sterically prevents efflux pump binding and ribosomal protection ✓

Explanation

Tetracycline resistance is mediated by Tet efflux pumps (e.g., Tet-A through Tet-E) and ribosomal protection proteins (e.g., TetM, TetO). Tigecycline's unique C-9 glycylamido substituent introduces steric bulk that prevents binding to the Tet efflux pump substrate site and prevents TetM-mediated ribosomal protection. It binds the same 30S ribosomal A site with higher affinity (5-fold greater than tetracycline for its cognate site) and is not ejected by these resistance mechanisms. However, tigecycline has poor bactericidal activity and is not suitable for bloodstream infections due to large Vd and low plasma levels.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.