Chitosan ameliorates Candida auris virulence in a Galleria mellonella infection model

Salomão Arias, L., Butcher, M. C., Short, B., McKloud, E., Delaney, C., Kean, R., Monteiro, D. R., Williams, C., Ramage, G. and Brown, J. L. (2020) Chitosan ameliorates Candida auris virulence in a Galleria mellonella infection model. Antimicrobial Agents and Chemotherapy, 64(8), e00476-20. (doi: 10.1128/AAC.00476-20) (PMID:32482674) (PMCID:PMC7526850)

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 vivo. In 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ramage, Professor Gordon and Kean, Mr Ryan and Brown, Dr Jason and Williams, Dr Craig and Delaney, Mr Christopher and McKloud, Emily
• Authors: Salomão Arias, L., Butcher, M. C., Short, B., McKloud, E., Delaney, C., Kean, R., Monteiro, D. R., Williams, C., Ramage, G., and Brown, J. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Antimicrobial Agents and Chemotherapy
• Publisher: American Society for Microbiology
• ISSN: 0066-4804
• ISSN (Online): 1098-6596
• Published Online: 01 June 2020
• Copyright Holders: Copyright © 2020 Arias et al.
• First Published: First published in Antimicrobial Agents and Chemotherapy 64(8):e00476-20.
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
173112		Understanding processes and mechanisms affecting the oral microbiome using OMICs approaches	Gordon Ramage	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/P504567/1	Med - Dental School