5-hydroxymethyl-2-furaldehyde from marine bacterium Bacillus subtilis inhibits biofilm and virulence of Candida albicans

Microbiol Res. 2018 Mar:207:19-32. doi: 10.1016/j.micres.2017.11.002. Epub 2017 Nov 8.

Abstract

Candida albicans is considered as the primary etiologic agent of candidiasis, a very common fungal infection in human. The yeast to hyphal transition and ability to form hypoxic biofilm on medical devices is well allied with virulence and antifungal resistance of C. albicans. Antagonistic agents that inhibit biofilm formation and alter susceptibility of C. albicans to conventional antifungals is of profound need. The present study explores the antibiofilm efficacy of Bacillus subtilis, a marine bacterial isolate from Palk Bay against C. albicans. Mass spectrometric analysis of ethyl acetate extract of B. subtilis unveiled 5-hydroxymethyl-2-furaldehyde (5HM2F) as one of its major components. 5HM2F demonstrated concentration dependent biofilm inhibition, which was also corroborated through microscopic analysis. Furthermore, 5HM2F was effective in inhibiting other virulence factors of C. albicans such as morphological transition and secreted hydrolases production. Fourier transform infrared spectroscopic analysis showed alteration in amide bond region. The reduction in ergosterol content and increased antifungal susceptibility was well allied with real time PCR result, which showed down regulation of genes involved in drug resistance mechanisms. In vivo study using Caenorhabditis elegans also substantiated the antivirulence efficacy of 5HM2F at in vivo condition. Thus, the present study reports the therapeutic potential of 5HM2F against C. albicans infections.

Keywords: 5-hydroxymethyl-2-furaldehyde; Antibiofilm activity; Antivirulence activity; Bacillus subtilis; Candida albicans; Yeast to hyphae.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Bacillus subtilis / metabolism*
  • Biofilms / drug effects*
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / pathogenicity
  • Candida albicans / drug effects*
  • Candida albicans / pathogenicity*
  • Clotrimazole / pharmacology
  • Drug Synergism
  • Ergosterol / metabolism
  • Furaldehyde / analogs & derivatives*
  • Furaldehyde / pharmacology
  • Hyphae / growth & development
  • Ketoconazole / pharmacology
  • Miconazole / pharmacology
  • Virulence / drug effects

Substances

  • Antifungal Agents
  • 5-hydroxymethylfurfural
  • Miconazole
  • Furaldehyde
  • Clotrimazole
  • Ketoconazole
  • Ergosterol