[PERSPECTIVES] 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 d-alanyl-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.

Source: Cold Spring Harbor perspectives in medicine - November 30, 2016 Category: Research Authors: Zeng, D., Debabov, D., Hartsell, T. L., Cano, R. J., Adams, S., Schuyler, J. A., McMillan, R., Pace, J. L. Tags: Antibiotics and Antibiotic Resistance PERSPECTIVES Source Type: research