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Daptomycin Pore Formation Is Restricted by Lipid Acyl Chain Composition.

Abstract：

:Daptomycin is a calcium-dependent lipopeptide antibiotic that is used clinically against various Gram-positive pathogens. It acts on bacterial cell membranes, whose susceptibility varies with the content of phosphatidylglycerol (PG). Some studies have reported that daptomycin permeabilizes and depolarizes bacterial cell membranes, while others have found no evidence of membrane permeabilization and thus proposed different mechanisms of antibacterial action. Divergent observations have also been reported regarding the effect of daptomycin on model membranes, which were found to be permeabilized nonselectively, selectively for small cations, or not at all. While these diverging model studies did consider the functional roles of different lipid head groups, they assumed that the acyl chains were interchangeable. We here show this assumption to be erroneous. In equimolar mixtures of PG and phosphatidylcholine (PC), dimyristoyl lipids support membrane permeabilization, whereas dioleyl and palmitoleyl lipids do not, even though daptomycin does bind to and form oligomers on all of these membranes. These observations help reconcile some of the discrepant findings in the literature.

journal_name

ACS Infect Dis

journal_title

ACS infectious diseases

authors

Taylor R,Beriashvili D,Taylor S,Palmer M

doi

10.1021/acsinfecdis.7b00138

subject

Has Abstract

pub_date

2017-11-10 00:00:00

pages

797-801

issue

11

issn

2373-8227

journal_volume

3

pub_type

杂志文章

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