The K4
peptide (
KKKKPLFGLFFGLF) was recently demonstrated to display good antimicrobial activities against various bacterial strains and thus represents a candidate for the treatment of multiple-
drug resistant
infections. In this study, we use various techniques to study K4 behaviour in different media: water, solutions of
detergent micelles,
phospholipid monolayers and
suspension of
phospholipid vesicles. First, self-assembly of the
peptide in water is observed, leading to the formation of spherical objects around 10nm in diameter. The addition of
micelles induces partial
peptide folding to an extent depending on the charge of the
detergent headgroups. The NMR structure of the
peptide in the presence of SDS displays a helical character of the hydrophobic moiety, whereas only partial folding is observed in DPC
micelles. This
peptide is able to destabilize the organization of monolayer membranes or bilayer
liposomes composed of anionic
lipids. When added on small
unilamellar vesicles it generates larger objects attributed to mixed
lipid-
peptide vesicles and aggregated vesicles. The absence of
calcein leakage from
liposomes, when adding K4, underlines the original mechanism of this linear amphipathic
peptide. Our results emphasize the importance of the electrostatic effect for K4 folding and
lipid destabilization leading to the microorganisms' death with a high selectivity for the eukaryotic cells at the MIC. Interestingly, the micrographs obtained by electronic microscopy after addition of
peptide on bacteria are also consistent with the formation of mixed
lipid-
peptide objects. Overall, this work supports a
detergent-like mechanism for the antimicrobial activity of this
peptide.