Oritavancin disrupts membrane integrity of Staphylococcus aureus and vancomycin-resistant enterococci to effect rapid bacterial killing.
Oritavancin is an investigational lipoglycopeptide in clinical development for the treatment of acute bacterial skin and skin structure infections. In this study, we demonstrate that oritavancin causes bacterial membrane depolarization and permeabilization leading to cell death of Gram-positive pathogens and that these effects are attributable to the 4'-chlorobiphenylmethyl group of the molecule.
Belley
Adam
A
The Medicines Company, 7170 Frederick Banting, St. Laurent, Quebec, Canada H4S 2A1. adam.belley@themedco.com
McKay
Geoffrey A
GA
Arhin
Francis F
FF
Sarmiento
Ingrid
I
Beaulieu
Sylvain
S
Fadhil
Ibthihal
I
Parr
Thomas R
TR
Moeck
Gregory
G
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D024881:Drug Resistance, Bacterial; D016983:Enterococcus / Q000187:drug effects*; D006020:Glycopeptides / Q000494:pharmacology*; D000077427:Lipoglycopeptides; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology* / Q000031:analogs & derivatives
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; D014640:Vancomycin; C100708:oritavancin