Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance

作者：Zeng Daina^*; Debabov Dmitri; Hartsell Theresa L; Cano Raul J; Adams Stacy; Schuyler Jessica A; McMillan Ronald; Pace John L

来源：Cold Spring Harbor Perspectives in Medicine, 2016, 6(12): a026989.

DOI：10.1101/cshperspect.a026989

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 cross-linking 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 methicillin-resistant 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.

• 出版日期2016-12