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.
Agile Sciences, Raleigh, North Carolina 27606.
Daina
D
Zeng
Emery Pharma Services, Emeryville, California 94608.
Dmitri
D
Debabov
Department of Anesthesiology/Critical Care Medicine, The Johns Hopkins School of Medicine and Nursing, Baltimore, Maryland 21287.
Theresa L
TL
Hartsell
ATCC Center for Translational Microbiology, Union, New Jersey 07083.|Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California 93407.
Raul J
RJ
Cano
Center for Skin Biology, GlaxoSmithKline, Durham, North Carolina 27703.
Stacy
S
Adams
ATCC Center for Translational Microbiology, Union, New Jersey 07083.
Jessica A
JA
Schuyler
ATCC Center for Translational Microbiology, Union, New Jersey 07083.
Ronald
R
McMillan
ATCC Center for Translational Microbiology, Union, New Jersey 07083.|STEM Program, Kean University, Union, New Jersey 07083.|Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, North Carolina 27707.
John L
JL
Pace
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002473:Cell Wall / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D006020:Glycopeptides / Q000737:chemistry / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects
D000900:Anti-Bacterial Agents; D006020:Glycopeptides
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