Effect of serine protease KEX2 on Candida albicans virulence under halogenated methyl sulfones

Future Microbiol. 2017 Mar:12:285-306. doi: 10.2217/fmb-2016-0141. Epub 2017 Feb 24.

Abstract

Aim: The effect of KEX2 mutations on C. albicans virulence and resistance to halogenated methyl sulfones was assessed.

Materials & methods: The mechanism of action of sulfones was studied using flow cytometry and microscopy. Expression of KEX2 and SAP5 was assessed using quantitative Real-Time-PCR. 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide and lactate dehydrogenase assays were elaborated to study, respectively, metabolism of Candida treated with sulfones and their cytotoxicity against tissues. Inflammatory response was detected by ELISA.

Results: Lysosome permeabilization and dose-dependent programmed cell death under sulfones were noted. KEX2 induction depended on halogenomethylsulfonyl groups, which affected cell wall biosynthesis and adhesion.

Conclusion: Sulfones treatment reduced Candida pathogenicity in Galleria mellonella. Sulfones are an alternative for antifungal therapies due to their safety profile and antibiofilm activity.

Keywords: C. albicans; adherence; host–pathogen interactions; pathogenesis; sulfones activity.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • Biofilms / drug effects
  • Candida albicans / drug effects*
  • Candida albicans / enzymology*
  • Candida albicans / genetics
  • Candida albicans / pathogenicity
  • Candidiasis / microbiology
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Dimethyl Sulfoxide / pharmacology*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Humans
  • Microbial Sensitivity Tests
  • Moths / microbiology
  • Serine Proteases / genetics
  • Serine Proteases / metabolism*
  • Sulfones / pharmacology*
  • Virulence / drug effects

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Sulfones
  • dimethyl sulfone
  • Serine Proteases
  • Dimethyl Sulfoxide