Daptomycin Pore Formation Is Restricted by Lipid Acyl
Chain Composition
Version 2 2017-10-23, 19:37
Version 1 2017-10-23, 19:35
Posted on 2017-10-23 - 19:37
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.
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Taylor, Robert; Beriashvili, David; Taylor, Scott; Palmer, Michael (2017). Daptomycin Pore Formation Is Restricted by Lipid Acyl
Chain Composition. ACS Publications. Collection. https://doi.org/10.1021/acsinfecdis.7b00138
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AUTHORS (4)
RT
Robert Taylor
DB
David Beriashvili
ST
Scott Taylor
MP
Michael Palmer