Structure, biochemistry and mechanism of action of glycopeptide antibiotics

  title={Structure, biochemistry and mechanism of action of glycopeptide antibiotics},
  author={Peter E. Reynolds},
  journal={European Journal of Clinical Microbiology and Infectious Diseases},
  • P. Reynolds
  • Published 1 November 1989
  • Biology, Chemistry
  • European Journal of Clinical Microbiology and Infectious Diseases
Glycopeptide antibiotics, including vancomycin and teicoplanin, are large, rigid molecules that inhibit a late stage in bacterial cell wall peptidoglycan synthesis. The three-dimensional structure contains a cleft into which peptides of highly specific configuration (L-aa-D-aa-D-aa) can fit: such sequences are found only in bacterial cell walls, hence glycopeptides are selectively toxic. Glycopeptides interact with peptides of this conformation by hydrogen bonding, forming stable complexes. As… 

Novel Mechanism of Resistance to Glycopeptide Antibiotics in Enterococcus faecium*

It is shown that bypass of the PBPs by the recently described β-lactam-insensitive l,d-transpeptidase from Enterococcus faecium (Ldtfm) can lead to high level resistance to glycopeptides and β- lactams.

Mechanism of Action of the Mannopeptimycins, a Novel Class of Glycopeptide Antibiotics Active against Vancomycin-Resistant Gram-Positive Bacteria

It was shown that mannopeptimycins interact with the membrane-bound cell wall precursor lipid II [C55-MurNAc-(peptide)-GlcNAc] and that this interaction is different from the binding of other lipid II-binding antibiotics such as vancomycin and mersacidin.

Evolution of peptidoglycan biosynthesis under the selective pressure of antibiotics in Gram-positive bacteria.

The role of antibiotics in selecting or counter-selecting diversification of the structure of peptidoglycan precursors and their mode of polymerization is focused on.

Mechanism of action of oritavancin and related glycopeptide antibiotics.

The antibacterial activity of oritavancin is described, the evidence supporting the proposed mechanism of action for this agent and related analogs are examined, and the evidence support the proposed mechanisms of action is examined.

Self-resistance mechanisms of actinomycetes producing lipid II-targeting antibiotics.

Structural Variations of the Cell Wall Precursor Lipid II and Their Influence on Binding and Activity of the Lipoglycopeptide Antibiotic Oritavancin

It is shown that amidation of the lipid II stem peptide predominantly accounts for the increased binding of oritavancin to the modified intermediates ending in d-Ala-d-Lac, thus partially explaining the low frequency of methicillin-resistant S. aureus acquiring high-level vancomycin resistance.

Mannopeptimycins, a novel class of glycopeptide antibiotics active against gram-positive bacteria

  • Hai-yin He
  • Biology, Chemistry
    Applied Microbiology and Biotechnology
  • 2004
The SAR data of the natural and synthetic esters demonstrate that the presence of hydrophobic groups near the terminal mannosyl moiety is critical for antibacterial potency, and suggest that the mannopeptimycins interfere with the late stages of bacterial cell wall biosynthesis.

Structure determination of peptides with antimicrobial action

Peptide antibiotics belonging to three different families were investigated using X-ray crystallography. The peptaibol antibiotics cephaibol A, B and C gave well-diffracting crystals and their



Teicoplanin, a new antibiotic from Actinoplanes teichomyceticus nov. sp

The mechanism of action of teicoplanin is discussed in comparison with those of other inhibitors of cell wall biosynthesis, namely, vancomycin, ristocetin, and gardimycin.

The structure and mode of action of glycopeptide antibiotics of the vancomycin group.

With the present knowledge of the structure and mode of action of the vancomycin group of antibiotics, it is fairly confident that they represent a group of compounds specifically evolved to aid the survival of the producing organisms by killing or inactivating competing gram-positive bacteria.

Modifications of the acyl-D-alanyl-D-alanine terminus affecting complex-formation with vancomycin.

Results throw some light on the specificity of the uptake of vancomycin by living bacteria.

Reversal by a Specific Peptide (Diacetyl-aoy-L-diaminobutyryl-D-alanyl-D-alanine) of Vancomycin Inhibition in Intact Bacteria and Cell-Free Preparations

Vancomycin inhibited the growth of Bacillus megaterium, Staphylococcus aureus and Micrococcus lysodeikticus, and in cell-free preparations from B. megaterium it inhibited the formation of mucopeptide

Specificity of combination between mucopeptide precursors and vancomycin or ristocetin.

  • H. Perkins
  • Biology, Chemistry
    The Biochemical journal
  • 1969
Vancomycin and ristocetin formed complexes on being mixed with mucopeptide precursors from various bacteria, as shown by chromatography, electrophoresis and differential ultraviolet spectra.

Reversal by a specific peptide (diacetyl-αγ-l-diaminobutyryl-d-alanine) of vancomycin inhibition in intact bacteria and cell-free preparations

Vancomycin inhibited the growth of Bacillus megaterium, Staphylococcus aureus and Micrococcus lysodeikticus, and in cell-free preparations from B. megaterium it inhibited the formation of mucopeptide

Effect of vancomycin on the synthesis of the cell wall mucopeptide of Staphylococcus aureus.

  • D. C. Jordan
  • Biology
    Biochemical and biophysical research communications
  • 1961

Studies on the mechanism of ristocetin-induced platelet agglutination. Effects of structural modification of ristocetin and vancomycin.

The mechanism by which ristocetin induces platelet agglutination in the presence of the von Willebrand factor was studied, suggesting both a binding requirement (mediated through phenolic groups) and a strong positive charge requirement for ristOCetin-induced agglUTination.

Inducible, transferable resistance to vancomycin in Enterococcus faecalis A256

It is concluded that Enterococcus faecalis A256 is resistant to glycopeptides by virtue of the synthesis of a 39-kDa cytoplasmic membrane protein, that this protein is probably involved in preventing access of the glycopesptides to their peptidoglycan targets, and that this resistance is transferable, probably by conjugation.

The preparation of iodinated vancomycin and its distribution in bacteria treated with the antibiotic.

Radioactive vancomycin was used to follow the fate of the antibiotic in bacteria that had been subjected to the least concentration required to inhibit growth and most of the radioactivity was in the cell walls, although some was found in the membrane fraction.