Host antimicrobial peptide S100A12 disrupts the fungal membrane by direct binding and inhibits growth and biofilm formation of Fusarium species

J Biol Chem. 2024 Mar;300(3):105701. doi: 10.1016/j.jbc.2024.105701. Epub 2024 Jan 30.

Abstract

Fungal keratitis is the foremost cause of corneal infections worldwide, of which Fusariumspp. is the common etiological agent that causes loss of vision and warrants surgical intervention. An increase in resistance to the available drugs along with severe side effects of the existing antifungals demands for new effective antimycotics. Here, we demonstrate that antimicrobial peptide S100A12 directly binds to the phospholipids of the fungal membrane, disrupts the structural integrity, and induces generation of reactive oxygen species in fungus. In addition, it inhibits biofilm formation by Fusariumspp. and exhibits antifungal property against Fusariumspp. both in vitro and in vivo. Taken together, our results delve into specific effect of S100A12 against Fusariumspp. with an aim to investigate new antifungal compounds to combat fungal keratitis.

Keywords: Fusarium; S100A12; antimicrobial peptide; biofilm; reactive oxygen species.

MeSH terms

  • Antifungal Agents* / metabolism
  • Antifungal Agents* / pharmacology
  • Biofilms* / drug effects
  • Cell Membrane* / drug effects
  • Eye Infections, Fungal / microbiology
  • Fusarium* / drug effects
  • Humans
  • Keratitis / microbiology
  • Phospholipids / metabolism
  • Reactive Oxygen Species / metabolism
  • S100A12 Protein* / metabolism
  • S100A12 Protein* / pharmacology

Substances

  • Antifungal Agents
  • S100A12 Protein
  • Phospholipids
  • Reactive Oxygen Species