Tigecycline overcomes tetracycline resistance mediated by Tet(M) and Tet(O) efflux pumps because:
- A Tigecycline is actively concentrated by bacterial tetracycline efflux pumps rather than expelled
- B The 9-t-butylglycylamide side chain at ring D sterically prevents recognition by Tet(M)/Tet(O) efflux proteins and ribosomal protection proteins ✓
- C Tigecycline binds irreversibly to 30S ribosomal RNA, unlike reversible tetracycline binding
- D Tigecycline is activated by bacterial β-lactamases to a form that bypasses efflux pumps
Explanation
Tigecycline is a glycylcycline derivative with a bulky 9-t-butylglycylamide substituent at position 9 of the tetracycline D ring. This modification sterically prevents recognition by both major tetracycline resistance mechanisms: (1) Tet efflux pumps (Tet(A)-(E) for classical tetracyclines) do not efficiently recognise and export tigecycline; (2) ribosomal protection proteins (Tet(M), Tet(O)) that normally dislodge tetracycline from the ribosome cannot effectively recognise the modified D-ring. Tigecycline retains 5-fold higher affinity for the ribosome than tetracycline.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.