The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes

2.50
Hdl Handle:
http://hdl.handle.net/10547/593506
Title:
The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes
Authors:
Junkes, Christof; Wessolowski, Axel; Farnaud, Sébastien; Evans, Robert W.; Good, Liam; Bienert, Michael; Dathe, Margitta
Abstract:
Cyclization of R- and W-rich hexapeptides has been found to enhance specifically the antimicrobial activity against Gram-negative Escherichia coli. To gain insight into the role of the bacterial outer membrane in mediating selectivity, we assayed the activity of cyclic hexapeptides derived from the parent sequence c-(RRWWRF) against several E. coli strains and Bacillus subtilis, L-form bacteria, and E. coli lipopolysaccharide (LPS) mutant strains, and we also investigated the peptide-induced permeabilization of the outer and inner membrane of E. coli. Wall-deficient L-form bacteria were distinctly less susceptible than the wild type strain. The patterns of peptide-induced permeabilization of the outer and inner E. coli membranes correlated well with the antimicrobial activity, confirming that membrane permeabilization is a detrimental effect of the peptides upon bacteria. Truncation of LPS had no influence on the activity of the cyclic parent peptide, but the highly active c-(RRWFWR), with three adjacent aromatic residues, required the complete LPS for maximal activity. Furthermore, differences in the activity of the parent peptide and its all-D sequence indicated stereospecific interactions with the LPS mutant strains. We suggest that, depending on the primary sequence of the peptides, either hydrophobic interactions with the fatty acid chains of lipid A, or electrostatic interactions disturbing the polar core region and interference with saccharide-saccharide interactions prevail in the barrier-disturbing effect upon the outer membrane and thereby provide peptide accessibility to the inner membrane. The results underline the importance of tryptophan and arginine residues and their relative location for a high antimicrobial effect, and the activity-modulating function of the outer membrane of E. coli. In addition to membrane permeabilization, the data provided evidence for the involvement of other mechanisms in growth inhibition and killing of bacteria.
Affiliation:
Leibniz Institute of Molecular Pharmacology; Westminster University; King's College London
Citation:
Junkes, C. et al (2008) 'The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes' J. Pept. Sci. 14 (4):535-43
Publisher:
Wiley
Journal:
Journal of peptide science : an official publication of the European Peptide Society
Issue Date:
Apr-2008
URI:
http://hdl.handle.net/10547/593506
DOI:
10.1002/psc.940
PubMed ID:
17985396
Additional Links:
http://onlinelibrary.wiley.com/doi/10.1002/psc.940/abstract
Type:
Article
Language:
en
ISSN:
1075-2617
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorJunkes, Christofen
dc.contributor.authorWessolowski, Axelen
dc.contributor.authorFarnaud, Sébastienen
dc.contributor.authorEvans, Robert W.en
dc.contributor.authorGood, Liamen
dc.contributor.authorBienert, Michaelen
dc.contributor.authorDathe, Margittaen
dc.date.accessioned2016-01-15T10:15:48Zen
dc.date.available2016-01-15T10:15:48Zen
dc.date.issued2008-04en
dc.identifier.citationJunkes, C. et al (2008) 'The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes' J. Pept. Sci. 14 (4):535-43en
dc.identifier.issn1075-2617en
dc.identifier.pmid17985396en
dc.identifier.doi10.1002/psc.940en
dc.identifier.urihttp://hdl.handle.net/10547/593506en
dc.description.abstractCyclization of R- and W-rich hexapeptides has been found to enhance specifically the antimicrobial activity against Gram-negative Escherichia coli. To gain insight into the role of the bacterial outer membrane in mediating selectivity, we assayed the activity of cyclic hexapeptides derived from the parent sequence c-(RRWWRF) against several E. coli strains and Bacillus subtilis, L-form bacteria, and E. coli lipopolysaccharide (LPS) mutant strains, and we also investigated the peptide-induced permeabilization of the outer and inner membrane of E. coli. Wall-deficient L-form bacteria were distinctly less susceptible than the wild type strain. The patterns of peptide-induced permeabilization of the outer and inner E. coli membranes correlated well with the antimicrobial activity, confirming that membrane permeabilization is a detrimental effect of the peptides upon bacteria. Truncation of LPS had no influence on the activity of the cyclic parent peptide, but the highly active c-(RRWFWR), with three adjacent aromatic residues, required the complete LPS for maximal activity. Furthermore, differences in the activity of the parent peptide and its all-D sequence indicated stereospecific interactions with the LPS mutant strains. We suggest that, depending on the primary sequence of the peptides, either hydrophobic interactions with the fatty acid chains of lipid A, or electrostatic interactions disturbing the polar core region and interference with saccharide-saccharide interactions prevail in the barrier-disturbing effect upon the outer membrane and thereby provide peptide accessibility to the inner membrane. The results underline the importance of tryptophan and arginine residues and their relative location for a high antimicrobial effect, and the activity-modulating function of the outer membrane of E. coli. In addition to membrane permeabilization, the data provided evidence for the involvement of other mechanisms in growth inhibition and killing of bacteria.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1002/psc.940/abstracten
dc.rightsArchived with thanks to Journal of peptide science : an official publication of the European Peptide Societyen
dc.subjectantimicrobial hexapeptidesen
dc.subjectcyclic peptidesen
dc.subjectlipopolysaccharides (LPS)en
dc.subjectL-form bacteriaen
dc.subjectmembrane permeabilizationen
dc.subjectouter membraneen
dc.subjectinner membraneen
dc.subject.meshAlanineen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshAntimicrobial Cationic Peptidesen
dc.subject.meshEscherichia colien
dc.subject.meshInhibitory Concentration 50en
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMutationen
dc.subject.meshOligopeptidesen
dc.subject.meshPeptides, Cyclicen
dc.subject.meshStructure-Activity Relationshipen
dc.subject.meshTime Factorsen
dc.subject.meshTryptophanen
dc.titleThe interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranesen
dc.typeArticleen
dc.contributor.departmentLeibniz Institute of Molecular Pharmacologyen
dc.contributor.departmentWestminster Universityen
dc.contributor.departmentKing's College Londonen
dc.identifier.journalJournal of peptide science : an official publication of the European Peptide Societyen
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