Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity

Nat Commun. 2017 Nov 8;8(1):1365. doi: 10.1038/s41467-017-01447-x.

Abstract

Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities of these assemblies have been largely overlooked. The recent identification of common characteristics shared by antibacterial and self-assembling peptides provides a paradigm shift towards development of antibacterial agents. Here we present the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers. The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization. We demonstrate the specificity of these membrane interactions and the development of antibacterial materials by integration of the peptide assemblies into tissue scaffolds. This study provides important insights into the significance of the interplay between self-assembly and antimicrobial activity and establishes innovative design principles toward the development of antimicrobial agents and materials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology*
  • Cell Membrane / drug effects
  • Circular Dichroism
  • Dipeptides / chemistry
  • Dipeptides / pharmacology*
  • Escherichia coli / drug effects
  • Gene Expression Regulation, Bacterial / drug effects
  • Glycylglycine / chemistry
  • Glycylglycine / pharmacology
  • HEK293 Cells
  • Humans
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Scanning
  • Nanostructures / chemistry*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / chemistry
  • Phenylalanine / pharmacology
  • Stress, Physiological / drug effects
  • Stress, Physiological / genetics
  • Tissue Scaffolds

Substances

  • Anti-Infective Agents
  • Dipeptides
  • diphenylalanine
  • Glycylglycine
  • Phenylalanine