J Bacteriol Virol.  2015 Jun;45(2):67-78. 10.4167/jbv.2015.45.2.67.

Glycopeptide Antibiotics: Structure and Mechanisms of Action

• Kang HK
• Park Y

• KMID: 2149207
• DOI: http://doi.org/10.4167/jbv.2015.45.2.67

Abstract

Glycopeptides of the clinically important antibiotic drugs are glycosylated cyclic or polycyclic nonribosomal peptides. Glycopeptides such as vancomycin and teicoplanin are often used for the treatment of gram-positive bacteria in patients. The increased incidence of drug resistance and inadequacy of these therapeutics against gram-positive bacterial infections would be the formation and clinical development of more variable second generation of glycopeptide antibiotics: semisynthetic lipoglycopeptide analogs such as telavancin, dalbavancin, and oritavancin with improved activity and better pharmacokinetic properties. In this review, we describe the development of and bacterial resistance to vancomycin, teicoplanin, and semisynthetic glycopeptides (teicoplanin, dalbavancin, and oritavancin). The clinical influence of resistance to glycopeptides, particularly vancomycin, are also discussed.

Keyword

Glycopeptide; Resistance; Vancomycin; Teicoplanin; Dalbavancin

MeSH Terms

Anti-Bacterial Agents*
Drug Resistance
Glycopeptides
Gram-Positive Bacteria
Gram-Positive Bacterial Infections
Humans
Incidence
Peptides
Teicoplanin
Vancomycin
Anti-Bacterial Agents
Glycopeptides
Peptides
Teicoplanin
Vancomycin

Figure

• 

  Figure 1. The chemical structure of glycopeptides. Vancomycin and teicoplanin are natural products. In teicoplanin, A2-1 through A2-5 denote the components of the complex that are characterized by a fatty-acid moiety at position R. Oritavancin and telavancin are semisynthetic second-generation glycopeptides from the vancomycin family. Dalbavancin is a semisynthetic derivative of teicoplanin.

• 

  Figure 2. Alignment of van resistance gene clusters from glycopeptide antibiotics-producing bacteria. Arrows indicate the direction of transcription. Empty arrow indicate hypothetical gene. A to N represent the D-Ala-D-Lac ligase giving name to the gene cluster. U, transcription regulator; R, regulator; S, histidine kinase; H, dehydrogenase; Y, D,D-carboxypeptidase; W and Z, unknown protein; vanXY, D,D-carboxypeptidase/D,D-dipeptidase; T, serine recemase.

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