Anticandidal activity of synthetic peptides: Mechanism of action revealed by scanning electron and fluorescence microscopies and synergism effect with nystatin

J Pept Sci. 2020 Jun;26(6):e3249. doi: 10.1002/psc.3249. Epub 2020 Mar 18.

Abstract

Candida albicans has emerged as a major public health problem in recent decades. The most important contributing factor is the rapid increase in resistance to conventional drugs worldwide. Synthetic antimicrobial peptides (SAMPs) have attracted substantial attention as alternatives and/or adjuvants in therapeutic treatments due to their strong activity at low concentrations without apparent toxicity. Here, two SAMPs, named Mo-CBP3 -PepI (CPAIQRCC) and Mo-CBP3 -PepII (NIQPPCRCC), are described, bioinspired by Mo-CBP3 , which is an antifungal chitin-binding protein from Moringa oleifera seeds. Furthermore, the mechanism of anticandidal activity was evaluated as well as their synergistic effects with nystatin. Both peptides induced the production of reactive oxygen species (ROS), cell wall degradation, and large pores in the C. albicans cell membrane. In addition, the peptides exhibited high potential as adjuvants because of their synergistic effects, by increasing almost 50-fold the anticandidal activity of the conventional antifungal drug nystatin. These peptides have excellent potential as new drugs and/or adjuvants to conventional drugs for treatment of clinical infections caused by C. albicans.

Keywords: Candida albicans; Mo-CBP3 peptides; anticandidal action; cell wall rupture; pore formation; synthetic antimicrobial peptide.

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Circular Dichroism
  • Electrons*
  • Erythrocytes / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Scanning
  • Microscopy, Fluorescence
  • Nystatin / chemical synthesis
  • Nystatin / chemistry
  • Nystatin / pharmacology*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*

Substances

  • Antifungal Agents
  • Peptides
  • Nystatin