Interaction of CAP18-Derived Peptides with Membranes Made from Endotoxins or Phospholipids

Abstract

Antimicrobial peptides with alpha-helical structures and positive net charges are in the focus of interest with regard to the development of new antibiotic agents, in particular against Gram-negative bacteria. Interaction between seven polycationic alpha-helical CAP18-derived peptides and different types of artificial membranes composed of phosphatidylcholine or lipopolysaccharide of the Gram-negative bacterium Escherichia coli were investigated using different biophysical techniques. Results obtained from fluorescence energy transfer spectroscopy with liposomes, monolayer measurements on a Langmuir trough, and electrophysiological measurements on planar reconstituted asymmetric bilayer membranes including the lipid matrix of the outer membrane of E. coli were correlated, and these data were, furthermore, correlated with structural parameters of the peptides (net charge, alpha-helical content, hydrophobic moment, and hydrophobicity). All peptides induced current fluctuations in planar membranes due to the formation of transient lesions above a peptide- and lipid-specific minimal clamp voltage. Antibacterial activity was exhibited only by those peptides that induced lesion formation in the reconstituted outer membrane at clamp voltages below the transmembrane potential of the natural membrane. Thus, we propose that the physicochemical properties of both the peptides as well as of the target membranes are important for antibacterial activity.

Extracellular Gelsolin Binds Lipoteichoic Acid and Modulates Cellular Response to Proinflammatory Bacterial Wall Components

“…This activity occurs stepwise, beginning with attachment to the outer membrane, which induces a conformational change in the peptide resulting in insertion into the membrane (37,(57)(58)(59). In our study we found that gelsolin had no effect on either the growth of Gram-positive and Gram-negative bacterial strains or on the antibacterial activity of cathelicidin-derived LL37.…”

Rationale for the Design of Shortened Derivatives of the NK-lysin-derived Antimicrobial Peptide NK-2 with Improved Activity against Gram-negative Pathogens

“…It is well established that LPS shields the bacteria and provides an effective barrier against hydrophilic and hydrophobic compounds (14,36). Thus, differences in activity against Gram-negative bacteria are likely to result from the interactions of peptides with LPS (37,38). Further studies are necessary to clarify this point.…”

Effects of Antimicrobial Peptides on Methanogenic Archaea

“…The AMPs tested in this study were derivatives of the human cathelicidin LL37 (LL20 and LL32) (41), derivatives of porcine NK-lysin (NK2 and C7S) (8), and a synthetic antilipopolysaccharide (anti-LPS) peptide, Lpep 19-2.5 (5). (All were purified from chemical peptide synthesis and kindly provided by O. Holst, Division of Structural Biochemistry, and J. Andrä, Division of Biophysics, Research Center Borstel, Borstel, Germany.)…”