Capsicum annuum L. trypsin inhibitor as a template scaffold for new drug development against pathogenic yeast

Antonie Van Leeuwenhoek. 2012 Mar;101(3):657-70. doi: 10.1007/s10482-011-9683-x. Epub 2011 Dec 8.

Abstract

A 6,000 Da peptide, named CaTI, was isolated from Capsicum annuum L. seeds and showed potent inhibitory activity against trypsin and chymotrypsin. The aim of this study was to determine the effect of CaTI on Saccharomyces cerevisiae, Candida albicans, Candida tropicalis and Kluyveromyces marxiannus cells. We observed that CaTI inhibited the growth of S. cerevisiae, K. marxiannus as well as C. albicans and induced cellular agglomeration and the release of cytoplasmic content. No effect on growth was observed in C. tropicalis but morphological changes were noted. In the spot assay, different degrees of sensitivity were shown among the strains and concentrations tested. Scanning electron microscopy showed that S. cerevisiae, K. marxiannus and C. albicans, in the presence of CaTI, exhibited morphological alterations, such as the formation of pseudohyphae, cellular aggregates and elongated forms. We also show that CaTI induces the generation of nitric oxide and interferes in a dose-dependent manner with glucose-stimulated acidification of the medium mediated by H(+)-ATPase of S. cerevisiae cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candida albicans / ultrastructure
  • Candida tropicalis / drug effects*
  • Candida tropicalis / growth & development
  • Candida tropicalis / ultrastructure
  • Capsicum / enzymology*
  • Cell Membrane Permeability / drug effects
  • Culture Media, Conditioned
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Evaluation, Preclinical
  • Fungal Proteins / antagonists & inhibitors
  • Glucose / pharmacology
  • Kluyveromyces / drug effects*
  • Kluyveromyces / growth & development
  • Kluyveromyces / ultrastructure
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Scanning
  • Nitric Oxide / biosynthesis
  • Plant Proteins / chemistry
  • Plant Proteins / isolation & purification
  • Plant Proteins / pharmacology*
  • Proton-Translocating ATPases / antagonists & inhibitors
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / ultrastructure
  • Trypsin Inhibitors / chemistry
  • Trypsin Inhibitors / isolation & purification
  • Trypsin Inhibitors / pharmacology*

Substances

  • Antifungal Agents
  • Culture Media, Conditioned
  • Fungal Proteins
  • Plant Proteins
  • Trypsin Inhibitors
  • Nitric Oxide
  • Proton-Translocating ATPases
  • Glucose