Antibacterial and Antibiofilm Properties of Self-Assembled Dipeptide Nanotubes

Over recent decades, multidrug-resistant pathogens have become a global concern, with WHO even considering it one of the biggest threats to global health, food security, and development today, which led to the search for alternative antibacterial agents. A special class is formed by peptides composed by the diphenylalanine motif whose antibacterial properties result from their supramolecular arrangement into nanotubes. However, several other dipeptides that also form nanotubes have been largely overlooked. Here, we present the antibacterial activity of four dipeptide nanotubes. The results point to diverse mechanisms through which dipeptide nanotubes exert their effect against bacteria. Antibacterial activity was similar for dipeptide nanotubes sufficiently wide to allow water flux while dipeptides displaying smaller channels were inactive. This suggests that two of the tested dipeptides, L-Phe-L-Phe (FF, diphenylalanine) and L-Leu-L-Ser (LS), are pore forming structures able to induce membrane permeation and affect cellular hydration and integrity. Of these two dipeptides, only FF demonstrated potential to inhibit biofilm formation. The amyloid-like nature and hydrophobicity of diphenylalanine assemblies are probably responsible for their adhesion to cell surfaces preventing biofilm formation and bacteria attachment.

Automated summary

In recent decades, multidrug-resistant pathogens have become a significant global concern, and alternative antibacterial agents are being sought. This study focuses on the antibacterial activity of four dipeptide nanotubes, revealing diverse mechanisms through which they exert their effect against bacteria. Two dipeptides, FF and LS, are identified as pore forming structures that induce membrane permeation and affect cellular hydration and integrity, with FF also showing potential in inhibiting biofilm formation due to its amyloid-like nature and hydrophobicity.