An Acyl-Linked Dimer of Daptomycin Is Strongly Inhibited by the Bacterial Cell Wall
Date
2017-03-28
Authors
Taylor, Robert
Scott, Bradley
Taylor, Scott D.
Palmer, Michael
Advisor
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Abstract
The lipopeptide antibiotic daptomycin is active against Gram-positive pathogens. It permeabilizes bacterial cell membranes, which involves the formation of membrane-associated oligomers. We here studied a dimer of daptomycin whose two subunits were linked through a bivalent aliphatic acyl chain. Unexpectedly, the dimer had very low activity on vegetative Staphylococcus aureus and Bacillus subtilis cells. However, activity resembled that of monomeric daptomycin on liposomes and on B. subtilis L-forms. These findings underscore the importance of the bacterial cell wall in daptomycin resistance.
Description
This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publi-cation in ACS Infectious Diseases,© American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/full/10.1021/acsinfecdis.7b00019.
Keywords
Antiobiotic resistance, Bacterial L-forms, Cell wall permeability, Lipopeptide antibiotics