Design, Synthesis, and Nanostructure-Dependent Antibacterial Activity of Cationic Peptide Amphiphiles

Nathalia Rodrigues De Almeida, Yuchun Han, Jesus Perez, Sydney Kirkpatrick, Yilin Wang, Martin Conda Sheridan

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The development of bacterial resistant strains is a global health concern. Designing antibiotics that limit the rise of pathogenic resistance is essential to efficiently treat pathogenic infections. Self-assembling amphiphilic molecules are an intriguing platform for the treatment of pathogens because of their ability to disrupt bacterial membranes and function as drug nanocarriers. We have designed cationic peptide amphiphiles (PAs) that can form micelles, nanofibers, and twisted ribbons with the aim of understanding antimicrobial activity at the supramolecular level. We have found that micelle-forming PAs possess excellent antimicrobial activity against various Gram-positive and Gram-negative pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Klebsiella pneumoniae with minimal inhibitory concentrations (MICs) ranging between 1 and 8 μg/mL, when compared to nanofibers with MICs >32 μg/mL. The data suggest that the antimicrobial activity of the PAs depends on their morphology, amino acid sequence, the length of the alkyl tail, and the overall hydrophobicity of the PA. Scanning electron microscopy, confocal microscopy, and flow cytometry studies using MRSA and Escherichia coli K12 strains showed that PAs increase cell membrane permeability and disrupt the integrity of pathogen's membrane, leading to cell lysis and death. PAs are a promising platform to develop new antimicrobials that could work as nanocarriers to develop synergistic antibacterial therapies.

Original languageEnglish (US)
Pages (from-to)2790-2801
Number of pages12
JournalACS Applied Materials and Interfaces
Volume11
Issue number3
DOIs
StatePublished - Jan 23 2019

Keywords

  • antimicrobials
  • cationic nanostructures
  • micelles
  • peptide amphiphiles
  • self-assembly
  • supramolecular structure-activity relationships

ASJC Scopus subject areas

  • Materials Science(all)

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