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dc.creatorYang, Lihua
dc.creatorGordon, Vernita D.
dc.creatorTrinkle, Dallas R.
dc.creatorSchmidt, Nathan W.
dc.creatorDavis, Matthew A.
dc.creatorDeVries, Clarabelle
dc.creatorSom, Abhigyan
dc.creatorCronan Jr., John E.
dc.creatorTew, Gregory N.
dc.creatorWong, Gerard C. L.
dc.date.accessioned2016-07-15T17:15:29Z
dc.date.available2016-07-15T17:15:29Z
dc.date.issued2008-12en
dc.identifierdoi:10.15781/T2WW7704K
dc.identifier.citationYang, Lihua, Vernita D. Gordon, Dallas R. Trinkle, Nathan W. Schmidt, Matthew A. Davis, Clarabelle DeVries, Abhigyan Som, John E. Cronan, Gregory N. Tew, and Gerard CL Wong. "Mechanism of a prototypical synthetic membrane-active antimicrobial: Efficient hole-punching via interaction with negative intrinsic curvature lipids." Proceedings of the National Academy of Sciences 105, no. 52 (2008): 20595-20600.en_US
dc.identifier.urihttp://hdl.handle.net/2152/39118
dc.descriptiona. Department of Materials Science and Engineering, d. Departments of Microbiology and Biochemistry, b. Department of Physics, e.Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801; and c. Department of Polymer Science and Engineering, University of Massachusetts, Amherst, MA 01003en_US
dc.description.abstractPhenylene ethynylenes comprise a prototypical class of synthetic antimicrobial compounds that mimic antimicrobial peptides produced by eukaryotes and have broad-spectrum antimicrobial activity. We show unambiguously that bacterial membrane permeation by these antimicrobials depends on the presence of negative intrinsic curvature lipids, such as phosphatidylethanolamine (PE) lipids, found in high concentrations within bacterial membranes. Plate-killing assays indicate that a PE-knockout mutant strain of Escherichia coli drastically out-survives the wild type against the membrane-active phenylene ethynylene antimicrobials, whereas the opposite is true when challenged with traditional metabolic antibiotics. That the PE deletion is a lethal mutation in normative environments suggests that resistant bacterial strains do not evolve because a lethal mutation is required to gain immunity. PE lipids allow efficient generation of negative curvature required for the circumferential barrel of an induced membrane pore; an inverted hexagonal HII phase, which consists of arrays of water channels, is induced by a small number of antimicrobial molecules. The estimated antimicrobial occupation in these water channels is nonlinear and jumps from 1 to 3 per 4 nmof induced water channel length as the global antimicrobial concentration is increased. By comparing to exactly solvable 1D spin models for magnetic systems, we quantify the cooperativity of these antimicrobials.en_US
dc.description.sponsorshipThis work was supported in part by National Science Foundation Grants DMR08–04363 and CBET08–27293, the Center of Advanced Materials for Purification of Water with Systems Science and Technology Centers, and the Rensselaer Polytechnic Institute-University of Illinois at Urbana-Champaign Nanoscale Science and Engineering Center, National Institutes of Health Grants R01-Al-074866 and R01 AI15650, and Office of Naval Research Grant N00014–03-1–0503.en_US
dc.language.isoengen_US
dc.publisherProceedings of the National Academy of Sciences of the U. S. A.en_US
dc.relation.ispartofUT Faculty/Researcher Worksen_US
dc.subjectlipidsen_US
dc.subjectPhenylene ethynylenesen_US
dc.subjectantimicrobial compoundsen_US
dc.subjectantibiotic resistant bacteriaen_US
dc.subjecthost defense peptidesen_US
dc.subjectinnate immunityen_US
dc.subjectprotein-membrane interactionsen_US
dc.titleMechanism of A Prototypical Synthetic Membrane-Active Antimicrobial: Efficient Hole-Punching by Targeting Lipids With Negative Spontaneous Curvature Lipidsen_US
dc.typeArticleen_US
dc.description.departmentMicrobiologyen_US
dc.rights.restrictionOpenen_US
dc.identifier.doi10.1073/pnas.0806456105


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