Alginate oligosaccharides modify hyphal infiltration of Candida albicans in an in vitro model of invasive human candidosis

J Appl Microbiol. 2017 Sep;123(3):625-636. doi: 10.1111/jam.13516. Epub 2017 Aug 1.

Abstract

Aims: A novel alginate oligomer (OligoG CF-5/20) has been shown to potentiate antifungal therapy against a range of fungal pathogens. The current study assessed the effect of this oligomer on in vitro virulence factor expression and epithelial invasion by Candida species.

Methods and results: Plate substrate assays and epithelial models were used to assess Candida albicans (CCUG 39343 and ATCC 90028) invasion, in conjunction with confocal laser scanning microscopy and histochemistry. Expression of candidal virulence factors was determined biochemically and by quantitative PCR (qPCR). Changes in surface charge of C. albicans following OligoG treatment were analysed using electrophoretic light scattering. OligoG induced marked alterations in hyphal formation in the substrate assays and reduced invasion in the epithelial model (P < 0·001). Significant dose-dependent inhibition of phospholipase activity in C. albicans was evident following OligoG treatment (P < 0·05). While OligoG binding failed to affect alterations in surface charge (P > 0·05), qPCR demonstrated a reduction in phospholipase B (PLB2) and SAPs (SAP4 and SAP6) expression.

Conclusion: OligoG CF-5/20 reduced in vitro virulence factor expression and invasion by C. albicans.

Significance and impact of the study: These results, and the previously described potentiation of antifungal activity, define a potential therapeutic opportunity in the treatment of invasive candidal infections.

Keywords: antimicrobials; biofilms; fungi; infection; virulence.

MeSH terms

  • Alginates / pharmacology*
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • Candida albicans / metabolism
  • Candidiasis / drug therapy
  • Candidiasis / microbiology*
  • Glucuronic Acid / pharmacology
  • Hexuronic Acids / pharmacology
  • Humans
  • Hyphae / drug effects
  • Hyphae / growth & development
  • Oligosaccharides / pharmacology*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Alginates
  • Antifungal Agents
  • Hexuronic Acids
  • Oligosaccharides
  • Virulence Factors
  • Glucuronic Acid

Supplementary concepts

  • Systemic candidiasis