Molecular interactions between supramolecular antibiotics and key components of bacterial cell walls

Eötvös Loránd Tudományegyetem

Biológia Doktori Iskola

Beke-Somfai Tamás

biológiai tudományok

The growing threat of antimicrobial resistance requires exploration toward new compounds with unique mechanisms of antibacterial action. Supramolecular assemblies combined with antimicrobial activity and potentially improved biostability could offer a promising alternative to current small molecule antibiotics. In this regard, peptidic large assemblies, composed of biostable non-natural amino acids, have the potential to deliver such agents. We have recently employed a design strategy focusing on an inducible assembly mechanism and utilized both cryo-electron microscopy and transmission electron microscopy (cryo-EM, TEM) to follow the formation of supramolecular peptide structures triggered by bacterial cell surface lipopolysaccharides (LPS). We designed lysine-rich heterochiral β3-peptides, with optimal residual spacing for enhanced coordination on the phosphate groups of LPS. [1]
Within this project the candidate will help deliver methodologies to further improve our understanding on interactions between key bacterial membrane components, i.e. LPS, and designed peptidic supramolecular antibiotics. These methods will enable screening of components which have strong affinity for binding core parts of LPS and similar compounds, which can be also used to initiate assembly of bactericid supramolecules.

[1] K. El Battioui, S. Chakraborty, A. Wacha, D. Molnár, M. Quemé-Peña, I. Cs. Szigyártó, Cs. L. Szabó, A. Bodor, K. Horváti, G. Gyulai, Sz. Bősze, J. Mihály, B. Jezsó, L. Románszki, J. Tóth, Z. Varga, I. Mándity, T. Juhász, T. Beke-Somfai: In situ captured antibacterial action of membrane incising peptide lamellae, Nat. Commun, 2024, 15, 3424

3 fő

HUN-REN TTK Magyar tudósok krt 2, 1117 Budapest

2026-05-31

English