Magainin 2 and PGLa are cationic, amphipathic antimicrobial peptides which when added as equimolar mixture exhibit a pronounced synergism in both their antibacterial and pore-forming activities. Here we show for the first time that the peptides assemble into defined supramolecular structures along the membrane interface. The resulting mesophases are quantitatively described by state-of-the art fluorescence self-quenching and correlation spectroscopies. Notably, the synergistic behavior of magainin 2 and PGLa correlates with the formation of hetero-domains and an order-of-magnitude increased membrane affinity of both peptides. Enhanced membrane association of the peptide mixture is only observed in the presence of phophatidylethanolamines but not of phosphatidylcholines, lipids that dominate bacterial and eukaryotic membranes, respectively. Thereby the increased membrane-affinity of the peptide mixtures not only explains their synergistic antimicrobial activity, but at the same time provides a new concept to increase the therapeutic window of combinatorial drugs.
- MeSH
- antibakteriální látky chemie izolace a purifikace farmakologie MeSH
- buněčná membrána chemie účinky léků MeSH
- ethanolaminy chemie MeSH
- fixní kombinace léků MeSH
- fluorescenční barviva chemie MeSH
- fluorescenční spektrometrie MeSH
- fosfatidylcholiny chemie MeSH
- fosfatidylethanolaminy chemie MeSH
- fosfatidylglyceroly chemie MeSH
- kationické antimikrobiální peptidy chemie izolace a purifikace farmakologie MeSH
- kůže chemie MeSH
- lipidové dvojvrstvy chemie MeSH
- magaininy chemie izolace a purifikace farmakologie MeSH
- proteiny Xenopus chemie izolace a purifikace farmakologie MeSH
- sloučeniny boru chemie MeSH
- synergismus léků MeSH
- vazba proteinů MeSH
- Xenopus laevis MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH