In situ captured antibacterial action of membrane-incising peptide lamellae

El Battioui, Kamal and Chakraborty, Sohini and Wacha, András Ferenc and Molnár, Dániel and Quemé Peña, Mayra and Szigyártó, Imola Csilla and Szabó, Csenge Lilla and Bodor, Andrea and Horváti, Kata and Gyulai, Gergő and Bősze, Szilvia and Mihály, Judith and Jezsó, Bálint and Románszki, Loránd and Tóth, Judit and Varga, Zoltán and Mándity, István and Juhász, Tünde and Beke-Somfai, Tamás (2024) In situ captured antibacterial action of membrane-incising peptide lamellae. NATURE COMMUNICATIONS, 15 (1). ISSN 2041-1723

Preview

Text elBattiouietal.-2024-Insitucapturedantibacterialactionofmembrane-.pdf - Published Version Available under License Creative Commons Attribution. Download (3MB) | Preview

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 β 3 -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.

Actions (login required)

Edit Item