Chitosan ameliorates Candida auris virulence in a Galleria mellonella infection model

Laís Salomão Arias, Mark C. Butcher, Bryn Short, Emily McKloud, Chris Delaney, Ryan Kean, Douglas Roberto Monteiro, Craig Williams, Gordon Ramage*, Jason L. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Candida auris has emerged as a multi-drug resistant nosocomial pathogen over the last decade. Outbreaks of the organism in healthcare facilities has resulted in life-threatening invasive candidiasis in over 40 countries worldwide. Resistance by C. auris to conventional antifungal drugs such as fluconazole and amphotericin B means that alternative therapeutics must be explored. As such, this study served to investigate the efficacy of a naturally derived polysaccharide called chitosan against aggregative (Agg) and non-aggregative (non-Agg) isolates of C. auris in vitro and in vivoIn vitro results indicated that chitosan was effective against planktonic and sessile forms of Agg and non-Agg C. auris. In a Galleria mellonella model to assess C. auris virulence, chitosan treatment was shown to ameliorate killing effects of both C. auris phenotypes (NCPF 8973 and NCPF 8978, respectively) in vivo Specifically, chitosan reduced the fungal load and increased survival rates of infected Galleria, whilst treatment alone was non-toxic to the larvae. Finally, chitosan treatment appeared to induce a stress-like gene expression response in NCPF 8973 in the larvae likely arising from a protective response by the organism to resist antifungal activity of the compound. Taken together, results from this study demonstrate that naturally derived compounds such as chitosan may be useful alternatives to conventional antifungals against C. auris.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Early online date1 Jun 2020
DOIs
Publication statusE-pub ahead of print - 1 Jun 2020

Keywords

  • Candida auris
  • pathogen
  • Galleria mellonella
  • antifungal activity

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    Arias, L. S., Butcher, M. C., Short, B., McKloud, E., Delaney, C., Kean, R., Monteiro, D. R., Williams, C., Ramage, G., & Brown, J. L. (2020). Chitosan ameliorates Candida auris virulence in a Galleria mellonella infection model. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/AAC.00476-20