Taylor, RobertScott, BradleyTaylor, Scott D.Palmer, Michael2017-04-132017-04-132017-03-28https://doi.org/10.1021/acsinfecdis.7b00019http://hdl.handle.net/10012/11662This 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.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.enAntiobiotic resistanceBacterial L-formsCell wall permeabilityLipopeptide antibioticsArticle