Approved glycopeptide antibacterial drugs: Mechanism of action and resistance
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.
Cold Spring Harbor Perspectives in Medicine
Zeng, Daina; Debabov, Dmitri; Hartsell, Theresa L.; Cano, Raul J.; Adams, Stacy; Schuyler, Jessica A.; McMillan, Ronald; and Pace, John L., "Approved glycopeptide antibacterial drugs: Mechanism of action and resistance" (2016). Kean Publications. 1800.