Characterization of daptomycin oligomerization with perylene excimer fluorescence: Stoichiometric binding of phosphatidylglycerol triggers oligomer formation
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Date
2012-03
Authors
Muraih, Jawad K.
Harris, Jesse
Taylor, Scott D.
Palmer, Michael
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Daptomycin is a lipopeptide antibiotic that binds to and depolarizes bacterial cell membranes. Its antibacterial activity requires calcium and correlates with the content of phosphatidylglycerol in the target membrane. Daptomycin has been shown to form oligomers on liposome membranes. We here use perylene excimer fluorescence to further characterize the membrane-associated oligomer. To this end, the N-terminal fatty acyl chain was replaced with perylene-butanoic acid. The perylene derivative retains one third of the antibacterial activity of native daptomycin. On liposomes containing phosphatidylcholine and phosphatidylglycerol, as well as on Bacillus subtilis cells, the perylene-labeled daptomycin forms excimers, which shows that the N-terminal acyl chains of neighboring oligomer subunits are in immediate contact with one another. In a lipid bicelle system, oligomer formation can be titrated with stoichiometric amounts of phosphatidylglycerol. Therefore, the interaction of daptomycin with a single molecule of phosphatidylglycerol is sufficient to trigger daptomycin oligomerization.
Description
The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.bbamem.2011.10.027 © 2012. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords
Bacillus-subtilis, Bactericidal activity, Daptomycin, Excimer fluorescence, Leads, Lipopeptide, ly146032, Membranes, Oligomerization, Perylene, Phosphatidylglycerol, Staphylococcus-aureus