Peptide from thaumatin plant protein exhibits selective anticandidal activity by inducing apoptosis via membrane receptor

Phytochemistry. 2019 Mar:159:46-55. doi: 10.1016/j.phytochem.2018.12.006. Epub 2018 Dec 19.

Abstract

Osmotin- and thaumatin-like proteins (OLPs and TLPs) have been associated with plant defense responses to different biotic stresses. In the present work, several in silico sequences from OLPs and TLPs were investigated by means of bioinformatics tools aiming to prospect for antimicrobial peptides. The peptide sequences chosen were further synthesized and characterized, and their activities and action mechanisms were assayed against some phytopathogenic fungi, bacteria and yeasts of clinical importance. From this survey approach, four peptide sequences (GDCKATSC, CPRALKVPGGCN, IVGQCPAKLKA, and CAADIVGQCPAKLK) were selected considering some chemical parameters commonly attributed to antimicrobial peptides. Antimicrobial assays showed that these peptides were unable to inhibit mycelial growth of phytopathogenic fungi and they did not affect bacterial cell growth. Nevertheless, significant inhibitory activity was found for CPRALKVPGGCN and CAADIVGQCPAKLK against Candida albicans and Saccharomyces cerevisiae. Fluorescence and scanning electron microscopy assays suggested that CAADIVGQCPAKLK did not damage the overall cell structure, or its activity was negligible on yeast membrane and cell wall integrity. However, it induced the production of reactive oxygen species (ROS) and apoptosis. Molecular docking analysis showed that CAADIVGQCPAKLK had strong affinity to interact with specific plasma membrane receptors of C. albicans and S. cerevisiae, which have been described as promoting the induction of apoptosis. The results indicate that CAADIVGQCPAKLK can be a valuable target for the development of a desired antimicrobial agent against the pathogen C. albicans.

Keywords: Candida; Saccharomyces; Yeast; human pathogens.

MeSH terms

  • Amino Acid Sequence
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Apoptosis / drug effects*
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candida albicans / metabolism
  • Cell Membrane / drug effects
  • Cell Wall / drug effects
  • Databases, Protein
  • Drug Discovery
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Plant Proteins / chemistry*
  • Plants / chemistry*
  • Reactive Oxygen Species / metabolism
  • Receptors, Cell Surface / drug effects*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism

Substances

  • Antifungal Agents
  • Peptides
  • Plant Proteins
  • Reactive Oxygen Species
  • Receptors, Cell Surface
  • thaumatin protein, plant