Article ; Online: Cyclic antimicrobial R-, W-rich peptides: the role of peptide structure and E. coli outer and inner membranes in activity and the mode of action.
European biophysics journal : EBJ
2011 Volume 40, Issue 4, Page(s) 515–528
Abstract: This study compares the effect of cyclic R-, W-rich peptides with variations ... A-, rough-LPS (r-LPS)- and smooth-LPS (s-LPS)-doped POPC liposomes demonstrated the decisive role of O ...
Abstract | This study compares the effect of cyclic R-, W-rich peptides with variations in amino acid sequences and sizes from 5 to 12 residues upon Gram negative and Gram positive bacteria as well as outer membrane-deficient and LPS mutant Escherichia coli (E. coli) strains to analyze the structural determinants of peptide activity. Cyclo-RRRWFW (c-WFW) was the most active and E. coli-selective sequence and bactericidal at the minimal inhibitory concentration (MIC). Removal of the outer membrane distinctly reduced peptide activity and the complete smooth LPS was required for maximal activity. c-WFW efficiently permeabilised the outer membrane of E. coli and promoted outer membrane substrate transport. Isothermal titration calorimetric studies with lipid A-, rough-LPS (r-LPS)- and smooth-LPS (s-LPS)-doped POPC liposomes demonstrated the decisive role of O-antigen and outer core polysaccharides for peptide binding and partitioning. Peptide activity against the inner E. coli membrane (IM) was very low. Even at a peptide to lipid ratio of 8/1, c-WFW was not able to permeabilise a phosphatidylglycerol/phosphatidylethanolamine (POPG/POPE) bilayer. Low influx of propidium iodide (PI) into bacteria confirmed a low permeabilising ability of c-WFW against PE-rich membranes at the MIC. Whilst the peptide effect upon eukaryotic cells correlated with the amphipathicity and permeabilisation of neutral phosphatidylcholine bilayers, suggesting a membrane disturbing mode of action, membrane permeabilisation does not seem to be the dominating antimicrobial mechanism of c-WFW. Peptide interactions with the LPS sugar moieties certainly modulate the transport across the outer membrane and are the basis of the E. coli selectivity of this type of peptides. |
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MeSH term(s) | Amino Acid Sequence ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Calorimetry ; Cell Membrane/chemistry ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cell Membrane Permeability/drug effects ; Chromatography, High Pressure Liquid ; Circular Dichroism ; Escherichia coli/chemistry ; Escherichia coli/metabolism ; Eukaryotic Cells/chemistry ; Eukaryotic Cells/metabolism ; Lipopolysaccharides/chemistry ; Lipopolysaccharides/metabolism ; Liposomes/chemistry ; Liposomes/metabolism ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Peptides, Cyclic/chemistry ; Peptides, Cyclic/pharmacology ; Phosphatidylethanolamines/chemistry ; Phosphatidylethanolamines/metabolism ; Phosphatidylglycerols/chemistry ; Phosphatidylglycerols/metabolism |
Chemical Substances | Anti-Infective Agents ; Lipopolysaccharides ; Liposomes ; Peptides, Cyclic ; Phosphatidylethanolamines ; Phosphatidylglycerols ; 1-palmitoyl-2-oleoylphosphatidylethanolamine (10015-88-0) |
Language | English |
Publishing date | 2011-02-01 |
Publishing country | Germany |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 283671-3 |
ISSN | 1432-1017 ; 0175-7571 |
ISSN (online) | 1432-1017 |
ISSN | 0175-7571 |
DOI | 10.1007/s00249-011-0671-x |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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