Short Synthetic α-Helical-Forming Peptide Amphiphiles for Fungal Keratitis Treatment In Vivo

Adv Healthc Mater. 2017 Mar;6(6). doi: 10.1002/adhm.201600777. Epub 2017 Jan 12.

Abstract

The emergence of fungal keratitis is on the rise globally. However, current antifungal therapeutics are ineffective in severe keratomycosis. Previously reported α-helical peptides comprising 8-14 amino acids demonstrate broad-spectrum antimicrobial activity both in vitro and in vivo. Here, α-helical peptides of the optimized sequences are investigated for antifungal biofilm in vitro and in vivo using a fungal biofilm-caused mouse keratitis model. The peptides with the optimal composition demonstrate higher α-helical propensity and improve antifungal activity in dispersing Candida albicans biofilm in vitro. Moreover, the optimized α-helical peptides are not only effective in treating C. albicans biofilm-induced keratitis in mice, they are also nontoxic to the mice eyes. These peptides have the potential to be developed as antifungal agents for the treatment of C. albicans biofilm-caused keratitis.

Keywords: antibiofilms; antibiotics resistance; antifungal; fungal keratitis; α-helical-forming peptides.

MeSH terms

  • Animals
  • Antifungal Agents* / chemistry
  • Antifungal Agents* / pharmacology
  • Antimicrobial Cationic Peptides* / chemistry
  • Antimicrobial Cationic Peptides* / pharmacology
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Candida albicans / physiology*
  • Candidiasis / drug therapy*
  • Disease Models, Animal
  • Keratitis* / drug therapy
  • Keratitis* / microbiology
  • Mice

Substances

  • Antifungal Agents
  • Antimicrobial Cationic Peptides