Effect of tryptophan position and lysine/arginine substitution in antimicrobial peptides on antifungal action

Biochem Biophys Res Commun. 2024 Apr 16:704:149700. doi: 10.1016/j.bbrc.2024.149700. Epub 2024 Feb 21.

Abstract

Every year, the overprescription, misuse, and improper disposal of antibiotics have led to the rampant development of drug-resistant pathogens and, in turn, a significant increase in the number of patients who die of drug-resistant fungal infections. Recently, researchers have begun investigating the use of antimicrobial peptides (AMPs) as next-generation antifungal agents to inhibit the growth of drug-resistant fungi. The antifungal activity of alpha-helical peptides designed using the cationic amino acids containing lysine and arginine and the hydrophobic amino acids containing isoleucine and tryptophan were evaluated using 10 yeast and mold fungi. Among these peptides, WIK-14, which is composed of a 14-mer with tryptophan sequences at the amino terminus, showed the best antifungal activity via transient pore formation and ROS generation. In addition, the in vivo antifungal effects of WIK-14 were investigated in a mouse model infected with drug-resistant Candida albicans. The results demonstrate the potential of AMPs as antifungal agents.

Keywords: Antimicrobial peptide; Drug-resistant Candida albicans; Membrane-permeable action; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology
  • Animals
  • Antifungal Agents* / chemistry
  • Antifungal Agents* / pharmacology
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Peptides
  • Arginine / chemistry
  • Candida albicans
  • Humans
  • Lysine / chemistry
  • Mice
  • Microbial Sensitivity Tests
  • Tryptophan* / chemistry

Substances

  • Antifungal Agents
  • Tryptophan
  • Lysine
  • Antimicrobial Peptides
  • Antimicrobial Cationic Peptides
  • Amino Acids
  • Arginine