Antibacterial and Antibiofilm Properties of Self-Assembled Dipeptide Nanotubes
Iris Soares1,2, Inês Rodrigues3,4, Paulo Martins da Costa3,4
1i3S-Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
Abstract:
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.
Insights
New dipeptide nanotubes show antibacterial properties by disrupting bacterial membranes. Diphenylalanine nanotubes also prevent biofilm formation, offering potential alternatives to antibiotics.
Area of Science:
- Biomaterials Science
- Microbiology
- Nanotechnology
Background:
- Multidrug-resistant pathogens pose a significant global health threat.
- Diphenylalanine nanotubes are known antibacterial agents due to their structure.
- Other dipeptide nanotubes remain largely unexplored for antibacterial potential.
Purpose of the Study:
- To investigate the antibacterial activity of four novel dipeptide nanotubes.
- To elucidate the mechanisms underlying their antibacterial effects.
- To assess their potential in combating multidrug-resistant bacteria and biofilm formation.
Main Methods:
- Synthesis and characterization of four distinct dipeptide nanotubes.
- Evaluation of antibacterial activity against various bacterial strains.
- Analysis of nanotube structure, including channel width and water flux.
- Assessment of biofilm inhibition and bacterial adhesion properties.
Main Results:
- Antibacterial activity correlated with nanotube channel width and water flux.
- L-Phe-L-Phe (FF) and L-Leu-L-Ser (LS) nanotubes exhibited pore-forming activity, inducing membrane permeation and affecting cellular hydration.
- FF nanotubes demonstrated significant inhibition of biofilm formation, likely due to their amyloid-like structure and hydrophobicity.
- Dipeptide nanotubes with smaller channels showed no significant antibacterial effect.
Conclusions:
- Dipeptide nanotubes represent a promising class of antibacterial agents with diverse mechanisms of action.
- Pore formation and disruption of cellular integrity are key antibacterial mechanisms for certain dipeptide nanotubes.
- Diphenylalanine nanotubes show dual functionality, exhibiting both direct antibacterial effects and anti-biofilm properties.
- The structural characteristics of dipeptide nanotubes, particularly channel width, are critical for their antibacterial efficacy.
