Cardiolipin Prevents Membrane Translocation and Permeabilization by Daptomycin

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dc.contributor.authorZhang, TianHua
dc.contributor.authorMuraih, Jawad K.
dc.contributor.authorTishbi, Nasim
dc.contributor.authorHerskowitz, Jennifer
dc.contributor.authorVictor, Rachel L.
dc.contributor.authorSilverman, Jared
dc.contributor.authorUwumarenogie, Stephanie
dc.contributor.authorTaylor, Scott D.
dc.contributor.authorPalmer, Michael
dc.contributor.authorMintzer, Evan
dc.date.accessioned2017-04-19T17:50:41Z
dc.date.available2017-04-19T17:50:41Z
dc.date.issued2014-04-25
dc.descriptionThis research was originally published in Journal of Biological Chemistry. Zhang, T., Muraih, J. K., Tishbi, N., Herskowitz, J., Victor, R. L., Silverman, J., … Mintzer, E. (2014). Cardiolipin Prevents Membrane Translocation and Permeabilization by Daptomycin. Journal of Biological Chemistry, 289(17), 11584–11591. © the American Society for Biochemistry and Molecular Biology." Available here: https://doi.org/10.1074/jbc.M114.554444en
dc.description.abstractDaptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcus species. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under the same conditions, daptomycin continues to form oligomers; however, these oligomers contain only close to four subunits, which is approximately half as many as observed on membranes without cardiolipin. The collective findings lead us to propose that a daptomycin pore consists of two aligned tetramers in opposite leaflets and that cardiolipin prevents the translocation of tetramers to the inner leaflet, thereby forestalling the formation of complete, octameric pores. Our findings suggest a possible mechanism by which cardiolipin may mediate resistance to daptomycin, and they provide new insights into the action mode of this important antibiotic.en
dc.identifier.urihttps://doi.org/10.1074/jbc.M114.554444
dc.identifier.urihttp://hdl.handle.net/10012/11680
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.subjectAntibiotic Resistanceen
dc.subjectAntibiotics actionen
dc.subjectCardiolipinen
dc.subjectFluorescenceen
dc.subjectIsothermal titration calorimetryen
dc.subjectLiposomesen
dc.subjectPhosphatidylglycerolen
dc.subjectLangmuir Monolayersen
dc.subjectLipopeptidesen
dc.subjectAntibiotic resistanceen
dc.titleCardiolipin Prevents Membrane Translocation and Permeabilization by Daptomycinen
dc.typeArticleen
dcterms.bibliographicCitationZhang, T., Muraih, J. K., Tishbi, N., Herskowitz, J., Victor, R. L., Silverman, J., … Mintzer, E. (2014). Cardiolipin Prevents Membrane Translocation and Permeabilization by Daptomycin. Journal of Biological Chemistry, 289(17), 11584–11591. https://doi.org/10.1074/jbc.M114.554444en
uws.contributor.affiliation1Faculty of Scienceen
uws.contributor.affiliation2Chemistryen
uws.peerReviewStatusRevieweden
uws.scholarLevelFacultyen
uws.typeOfResourceTexten

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