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- Title
In situ captured antibacterial action of membrane-incising peptide lamellae.
- Authors
el Battioui, Kamal; Chakraborty, Sohini; Wacha, András; Molnár, Dániel; Quemé-Peña, Mayra; Szigyártó, Imola Cs.; Szabó, Csenge Lilla; Bodor, Andrea; Horváti, Kata; Gyulai, Gergő; Bősze, Szilvia; Mihály, Judith; Jezsó, Bálint; Románszki, Loránd; Tóth, Judit; Varga, Zoltán; Mándity, István; Juhász, Tünde; Beke-Somfai, Tamás
- Abstract
Developing unique mechanisms of action are essential to combat the growing issue of antimicrobial resistance. Supramolecular assemblies combining the improved biostability of non-natural compounds with the complex membrane-attacking mechanisms of natural peptides are promising alternatives to conventional antibiotics. However, for such compounds the direct visual insight on antibacterial action is still lacking. Here we employ a design strategy focusing on an inducible assembly mechanism and utilized electron microscopy (EM) to follow the formation of supramolecular structures of lysine-rich heterochiral β3-peptides, termed lamellin-2K and lamellin-3K, triggered by bacterial cell surface lipopolysaccharides. Combined molecular dynamics simulations, EM and bacterial assays confirmed that the phosphate-induced conformational change on these lamellins led to the formation of striped lamellae capable of incising the cell envelope of Gram-negative bacteria thereby exerting antibacterial activity. Our findings also provide a mechanistic link for membrane-targeting agents depicting the antibiotic mechanism derived from the in-situ formation of active supramolecules. Inspired by the alternating chirality backbone pattern of some effective peptide antimicrobials, here authors design lysine-rich heterochiral peptides that show antimicrobial activity.
- Subjects
PEPTIDES; BACTERIAL cell surfaces; COMPLEX compounds; SUPRAMOLECULES; MOLECULAR dynamics; PEPTIDE antibiotics
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-47708-4