Assembly of cationic and amphiphilic β-sheet FKF tripeptide confers antibacterial activity

Ziv Azoulay, Polina Aibinder, Ayala Gancz, Jacob Moran-Gilad, Shiri Navon-Venezia, Hanna Rapaport

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The race drawn against bacteria facing the evolution of antimicrobial resistance fuels research for new drugs and therapeutic strategies. FKF, a tripeptide that is cationic and amphiphilic was examined in light of its potential antimicrobial activity. Acid titration of purified peptide solution, 6% w/v (136 mM), yielded a hydrogel at pH~ 4. Cryo-TEM images of FKF revealed distinct phases formed upon increase in pH, ranging from elongated needles, uniform width fibers, sheets and tubular structures. 1H NMR attested FKF charged states as function of pH, and CD and FTIR measurements indicated that FKF β-sheet assemblies are held by both π-π stacking and H-bonds. FKF hydrogel displayed bactericidal activity against E. coli and P. aeruginosa with a 3-log reduction in bacterial counts. The hydrogel was also found effective in reducing P. aeruginosa contamination in a skin lesion model in rats. FKF forms a unique antimicrobial peptide-hydrogel, showing neglectable effect in dissolved state, yet only when fibrillary assembled it gains functionality. Statement of Significance: Ultra-short peptides are at the frontier of peptide self-assembly research. The tripeptide FKF assumes distinct assembly forms that are a function of pH, for which we have pinpointed the accompanying changes in charge. Made of natural amino acids, FKF forms a pure peptide hydrogel phase, which is intrinsically antimicrobial. We demonstrate that antimicrobial effect is only assumed by the peptide assemblies, posing self-assembly as a pre-requisite for FKF's bactericidal effect. This system provides evidence for the link between specific microscopic peptide assembled structures, macroscopic gel formation and antimicrobial effect, utilized to alleviate bacterial contamination in vivo.

Original languageEnglish
Pages (from-to)231-241
Number of pages11
JournalActa Biomaterialia
Volume125
DOIs
StatePublished - 15 Apr 2021

Keywords

  • Antimicrobial peptide
  • Peptide self assembly
  • Pseudomonas aeruginosa
  • peptide hydrogel

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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