Teicoplanin Mode of Action
Teicoplanin inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors, preventing both glycan chain polymerization and transpeptidation reactions essential for cell wall integrity. 1
Mechanism of Cell Wall Inhibition
Teicoplanin, like other glycopeptide antibiotics, acts through a unique mechanism that targets late-stage peptidoglycan synthesis outside the bacterial cell membrane 2, 1:
The drug binds specifically to L-amino acid-D-alanine-D-alanine (L-aa-D-Ala-D-Ala) sequences found exclusively in bacterial cell wall intermediates, forming stable complexes through hydrogen bonding 1
This binding occurs via a cleft in teicoplanin's three-dimensional structure that accommodates peptides of highly specific configuration, explaining its selective toxicity against bacteria 1
The bulky teicoplanin-substrate complex sterically hinders peptidoglycan polymerase, preventing the enzyme from catalyzing formation of backbone glycan chains from wall subunits as they are extruded through the cytoplasmic membrane 1
Subsequent transpeptidation reactions that cross-link peptidoglycan strands are also blocked, preventing the cell wall from achieving structural rigidity 1
Resistance Profile
The mechanism confers important resistance characteristics 1:
Resistance development is more difficult compared to other antibiotic classes because the drug binds directly to the substrate (peptidoglycan precursor) rather than to an enzyme active site 1
The inhibitor must bind outside the membrane to prevent proper alignment of two separate enzyme active sites, making simple enzymatic modifications insufficient for resistance 1
However, resistance has been reported with coagulase-negative staphylococci in clinical practice 2
Structural Distinctions from Vancomycin
While teicoplanin shares the same fundamental mechanism as vancomycin, key structural differences affect its clinical properties 2, 3:
Teicoplanin is 50 to 100 times more lipophilic than vancomycin due to fatty-acid components attached to its aglycone structure 2
This increased lipophilicity allows for intramuscular administration and once-daily dosing, unlike vancomycin which requires intravenous infusion 4, 3
Tissue penetration is enhanced, with high concentrations achieved in lung and bone tissue 3