Antifungal activity of phlorotannins against dermatophytes and yeasts: approaches to the mechanism of action and influence on Candida albicans virulence factor

PLoS One. 2013 Aug 12;8(8):e72203. doi: 10.1371/journal.pone.0072203. eCollection 2013.

Abstract

In the last few decades, fungal infections, particularly nosocomial, increased all around the world. This increment stimulated the search for new antifungal agents, especially those derived from nature. Among natural products, those from marine sources have gained prominence in the last years. Purified phlorotannins extracts from three brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus) were screened for their antifungal activity against human pathogenic yeast and filamentous fungi. The purified phlorotannins extracts from the studied seaweeds displayed fungistatic and fungicidal activity against yeast and dermatophytes, respectively, pointing to their interest as anti-dermatophyte agent. C. albicans ATCC 10231 was the most susceptible among yeast, while Epidermophyton floccosum and Trichophyton rubrum were the most susceptible among dermatophytes. Since the antifungal mechanism constitutes an important strategy for limiting the emergence of resistance to the commercially available agents, the mechanism of action of purified phlorotannins extracts was approached. C. nodicaulis and C. usneoides seem to act by affecting the ergosterol composition of the cell membrane of yeast and dermatophyte, respectively. F. spiralis influenced the dermatophyte cell wall composition by reducing the levels of chitin. Phlorotannins also seem to affect the respiratory chain function, as all of the studied species significantly increased the activity of mitochondrial dehydrogenases and increased the incorporation of rhodamine 123 by yeast cells. Phlorotannins from F. spiralis inhibited the dimorphic transition of Candida albicans, leading to the formation of pseudohyphae with diminished capacity to adhere to epithelial cells. This finding is associated with a decrease of C. albicans virulence and capacity to invade host cells and can be potentially interesting for combined antifungal therapy, namely for the control of invasive candidiasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Arthrodermataceae / drug effects*
  • Arthrodermataceae / metabolism
  • Candida albicans / drug effects
  • Candida albicans / metabolism
  • Candida albicans / pathogenicity
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Seaweed / chemistry
  • Tannins / pharmacology*
  • Virulence Factors
  • Yeasts / drug effects*
  • Yeasts / metabolism

Substances

  • Antifungal Agents
  • Plant Extracts
  • Tannins
  • Virulence Factors

Grant support

The authors are grateful to Fundação para a Ciência e a Tecnologia (FCT) through grant no. PEst-C/EQB/LA0006/2011 and no. Pest-OE/SAV/UI4040/2011. G. Lopes (SFRH/BD/61565/2009) is indebted to FCT, Fundo Social Europeu (FSE) and Programa Operacional Potencial Humano (POPH) for the grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.