Restraining Pathogenicity in Candida albicans by Taxifolin as an Inhibitor of Ras1-pka Pathway

Mycopathologia. 2017 Dec;182(11-12):953-965. doi: 10.1007/s11046-017-0170-4. Epub 2017 Jul 5.

Abstract

Candida albicans is one of the most virulent and opportunistic fungal strains. In the present scenario, majority metabolic imbalances and unsuccessful treatments of some severe diseases including cancer, diabetes, HIV, psoriasis are because of invasive Candida emergence. Being a beneficial integral part of human biome, its elimination is not possible. The major pathogenicity characteristics in Candida involve hyphal growth, biofilm formation, HSP90 down regulation and genetic modifications. Ras1-pka pathway initiated by HSP90 down regulation is important for hyphal growth and has been focused in the present study. The principle transcriptional factors that induce hyphal growth causing invasiveness and virulence through this pathway have been identified as Tec1 and Rfg1. In the present study, taxifolin, a naturally occurring polyphenol, has been identified as inhibitor for both the transcriptional factors in parallel.

Keywords: Biome; C. albicans; Pathogenicity; Ras1-pka pathway; Rfg1; Tec1.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Binding Sites
  • Candida albicans / drug effects
  • Candida albicans / pathogenicity*
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Catalytic Domain
  • DNA-Binding Proteins / antagonists & inhibitors*
  • Fungal Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / biosynthesis
  • Humans
  • Hyphae / growth & development
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • Repressor Proteins / antagonists & inhibitors*
  • Transcription Factors / antagonists & inhibitors*
  • ras Proteins / antagonists & inhibitors

Substances

  • Antifungal Agents
  • DNA-Binding Proteins
  • Fungal Proteins
  • HSP90 Heat-Shock Proteins
  • RFG1 protein, Candida albicans
  • Repressor Proteins
  • TEC1 protein, Candida albicans
  • Transcription Factors
  • Quercetin
  • taxifolin
  • ras Proteins