Interaction of Daptomycin with Lipid Bilayers Correlated to Its Action on Cell Membranes

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dc.contributor.advisorHuang, Huey W.
dc.contributor.committeeMemberToffoletto, Frank R.
dc.contributor.committeeMemberKillian, Thomas C.
dc.creatorChen, Yen-Fei
dc.date.accessioned2014-08-07T20:07:09Z
dc.date.available2014-08-07T20:07:09Z
dc.date.created2013-12
dc.date.issued2013-05-31
dc.date.submittedDecember 2013
dc.date.updated2014-08-07T20:07:10Z
dc.description.abstractDaptomycin is a lipopeptide antibiotic notably against multidrug-resistant, gram-positive pathogens. Evidence shows that the antibiotic acts neither on DNA nor on the proteins. It has been shown to insert and aggregate in the bacteria membrane; nevertheless, how the molecular interaction leads to cell death is unknown. In this work, the physical properties of interactions between daptomycin and model membranes are studied in order to understand the underlying mechanism of daptomycin. First, daptomycin’s binding affinity to membranes was found to be proportional to Ca++ concentration. The effect of Ca++ cannot be replaced by other divalent ions such as Mg++. After binding, daptomycin was found to form lipid-peptide aggregations on phosphatidylglycerol(PG)-containing vesicles. PG is required for the formation of lipid-peptide aggregates, which eventually lead to membrane ruptures. Cardiolipin, another main component in bacterial membrane, cannot substitute PG to induce the same membrane defect. In addition, with a fixed concentration of Ca++, it requires a minimum concentration of daptomycin to trigger the membrane defect process. The membrane defect results mainly from lipid-peptide aggregations rather than from pores forming in the membrane. Finally, x-ray data imply that daptomycin binds to the headgroup region of the bilayer, which causes membrane thinning. The elastic energy of membrane thinning elevates the energy level of the daptomycin binding state, which explains the transition to the aggregation state.
dc.format.mimetypeapplication/pdf
dc.identifier.citationChen, Yen-Fei. "Interaction of Daptomycin with Lipid Bilayers Correlated to Its Action on Cell Membranes." (2013) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/76483">https://hdl.handle.net/1911/76483</a>.
dc.identifier.urihttps://hdl.handle.net/1911/76483
dc.language.isoeng
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.subjectMembrane
dc.subjectDaptomycin
dc.subjectAntimicrobial peptides
dc.subjectGUV
dc.titleInteraction of Daptomycin with Lipid Bilayers Correlated to Its Action on Cell Membranes
dc.typeThesis
dc.type.materialText
thesis.degree.departmentPhysics and Astronomy
thesis.degree.disciplineNatural Sciences
thesis.degree.grantorRice University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science
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