Approved glycopeptide antibacterial drugs: Mechanism of action and resistance

Daina Zeng, Dmitri Debabov, Theresa L. Hartsell, Raul J. Cano, Stacy Adams, Jessica A. Schuyler, Ronald McMillan, John L. Pace

Research output: Contribution to journalArticlepeer-review

Abstract

The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the Dalanyl- D-alanine terminus of the lipid II bacterial cell-wall precursor, preventing crosslinking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillinresistant Staphylococcus aureus and of susceptible Enterococcus spp. Newer lipoglycopeptide derivatives (telavancin, dalbavancin, and oritavancin) were designed in a targeted fashion to increase antibacterial activity, in some cases through secondary mechanisms of action. Resistance to the glycopeptides emerged in delayed fashion and occurs via a spectrum of chromosome- and plasmid-associated elements that lead to structural alteration of the bacterial cell-wall precursor substrates.

Original languageEnglish (US)
Article numbera026989
JournalCold Spring Harbor Perspectives in Medicine
Volume6
Issue number12
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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