Highly synergistic antimicrobial activity of magainin 2 and PGLa peptides is rooted in the formation of supramolecular complexes with lipids

0531413 - ÚFCH JH 2021 RIV GB eng J - Journal Article
Aisenbrey, Ch. - Amaro, Mariana - Pospíšil, Petr - Hof, Martin - Bechinger, B.
Highly synergistic antimicrobial activity of magainin 2 and PGLa peptides is rooted in the formation of supramolecular complexes with lipids.
Scientific Reports. Roč. 10, č. 1 (2020), č. článku 11652. ISSN 2045-2322. E-ISSN 2045-2322
R&D Projects: GA ČR(CZ) GX19-26854X
Institutional support: RVO:61388955
Keywords : xenopus-laevis * membranes * bilayers * family * model * permeability * enhancement * mechanism * diffusion * topology
OECD category: Physical chemistry
Impact factor: 4.380, year: 2020
Method of publishing: Open access

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.
Permanent Link: http://hdl.handle.net/11104/0310078