Response of Paracoccidioides lutzii to the antifungal camphene thiosemicarbazide determined by proteomic analysis

Future Microbiol. 2018 Oct:13:1473-1496. doi: 10.2217/fmb-2018-0176. Epub 2018 Oct 12.

Abstract

Aim: To perform the proteomic profile of Paracoccidioides lutzii after treatment with the compound camphene thiosemicarbazide (TSC-C) in order to study its mode of action.

Methods: Proteomic analysis was carried out after cells were incubated with TSC-C in a subinhibitory concentration. Validation of the proteomic results comprised the azocasein assay, western blot and determination of the susceptibility of a mutant to the compound.

Results: Proteins related to metabolism, energy and protein fate were regulated after treatment. In addition, TSC-C reduces the proteolytic activity of the protein extract similarly to different types of protease inhibitors.

Conclusion: TSC-C showed encouraging antifungal activity, working as a protease inhibitor and downregulating important pathways impairing the ability of the fungi cells to produce important precursors.

Keywords: Paracoccidioides; antifungal; camphene thiosemicarbazide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Bicyclic Monoterpenes
  • Cell Extracts / analysis
  • Fungal Proteins / analysis
  • Gene Expression Regulation, Fungal / drug effects
  • Gene Expression Regulation, Fungal / genetics
  • Mutation
  • Paracoccidioides / drug effects*
  • Paracoccidioides / genetics
  • Protease Inhibitors / pharmacology
  • Proteomics*
  • Semicarbazides / pharmacology*
  • Terpenes / pharmacology*

Substances

  • Antifungal Agents
  • Bicyclic Monoterpenes
  • Cell Extracts
  • Fungal Proteins
  • Protease Inhibitors
  • Semicarbazides
  • Terpenes
  • thiosemicarbazide
  • camphene