Multimerization of a proline-rich antimicrobial peptide, Chex-Arg20, alters its mechanism of interaction with the Escherichia coli membrane

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dc.contributor.authorLi, W.
dc.contributor.authorO'Brien-Simpson, N.
dc.contributor.authorTailhades, J.
dc.contributor.authorPantarat, N.
dc.contributor.authorDawson, R.
dc.contributor.authorOtvos, L.
dc.contributor.authorReynolds, E.
dc.contributor.authorSeparovic, F.
dc.contributor.authorHossain, M.
dc.contributor.authorWade, J.
dc.date.issued2015
dc.description.abstractA3-APO, a de novo designed branched dimeric proline-rich antimicrobial peptide (PrAMP), is highly effective against a variety of in vivo bacterial infections. We undertook a selective examination of the mechanism for the Gram-negative Escherichia coli bacterial membrane interaction of the monomer (Chex-Arg20), dimer (A3-APO), and tetramer (A3-APO disulfide-linked dimer). All three synthetic peptides were effective at killing E. coli. However, the tetramer was 30-fold more membrane disruptive than the dimer while the monomer showed no membrane activity. Using flow cytometry and high-resolution fluorescent microscopy, it was observed that dimerization and tetramerization of the Chex-Arg20 monomer led to an alteration in the mechanism of action from non-lytic/membrane hyperpolarization to membrane disruption/depolarization. Our findings show that the membrane interaction and permeability of Chex-Arg20 was altered by multimerization.
dc.description.statementofresponsibilityWenyi Li, Neil M. O'Brien-Simpson, Julien Tailhades, Namfon Pantarat, Raymond M. Dawson, Laszlo Otvos, Eric C. Reynolds, Frances Separovic, Mohammed Akhter Hossain, John D. Wade
dc.identifier.citationChemistry and Biology, 2015; 22(9):1250-1258
dc.identifier.doi10.1016/j.chembiol.2015.08.011
dc.identifier.issn1074-5521
dc.identifier.issn1879-1301
dc.identifier.urihttp://hdl.handle.net/2440/99150
dc.language.isoen
dc.publisherElsevier (Cell Press)
dc.relation.granthttp://purl.org/au-research/grants/arc/DP150103522
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1029878
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1008106
dc.rights© 2015 Elsevier Ltd. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.chembiol.2015.08.011
dc.subjectEscherichia coli
dc.subjectProline
dc.subjectPeptides
dc.subjectAntimicrobial Cationic Peptides
dc.subjectMembrane Proteins
dc.subjectMicroscopy, Fluorescence
dc.subjectFlow Cytometry
dc.subjectMicrobial Sensitivity Tests
dc.subjectStructure-Activity Relationship
dc.subjectDimerization
dc.subjectProline-Rich Protein Domains
dc.titleMultimerization of a proline-rich antimicrobial peptide, Chex-Arg20, alters its mechanism of interaction with the Escherichia coli membrane
dc.typeJournal article
pubs.publication-statusPublished

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