{Reference Type}: Journal Article
{Title}: In situ captured antibacterial action of membrane-incising peptide lamellae.
{Author}: El Battioui K;Chakraborty S;Wacha A;Molnár D;Quemé-Peña M;Szigyártó IC;Szabó CL;Bodor A;Horváti K;Gyulai G;Bősze S;Mihály J;Jezsó B;Románszki L;Tóth J;Varga Z;Mándity I;Juhász T;Beke-Somfai T;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Apr 23
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-47708-4
{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.