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

Christof Junkes, Axel Wessolowski, Sebastien Farnaud, Robert W. Evans, Liam Good, Michael Bienet, Margitta Dathe

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)535-543
Number of pages9
JournalJournal of Peptide Science
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Fingerprint

Tryptophan
Escherichia coli
Arginine
Membranes
Peptides
Lipopolysaccharides
Bacteria
L Forms
Cold Climate
Cyclic Peptides
Lipid A
Cyclization
Bacilli
Coulomb interactions
Bacillus subtilis
Static Electricity
Hydrophobic and Hydrophilic Interactions
Fatty Acids
Growth

Keywords

  • Antimicrobial hexapeptides
  • Cyclic peptides
  • Inner membrane
  • L-form bacteria
  • Lipopolysaccharides (LPS)
  • Membrane permeabilization
  • Outer membrane

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes. / Junkes, Christof; Wessolowski, Axel; Farnaud, Sebastien; Evans, Robert W.; Good, Liam; Bienet, Michael; Dathe, Margitta.

In: Journal of Peptide Science, Vol. 14, No. 4, 04.2008, p. 535-543.

Research output: Contribution to journalArticle

Junkes, Christof ; Wessolowski, Axel ; Farnaud, Sebastien ; Evans, Robert W. ; Good, Liam ; Bienet, Michael ; Dathe, Margitta. / The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes. In: Journal of Peptide Science. 2008 ; Vol. 14, No. 4. pp. 535-543.
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