Chitosan Ameliorates Candida auris Virulence in a Galleria mellonella Infection Model

Abstract

Candida auris has emerged as a multidrug-resistant nosocomial pathogen over the last decade. Outbreaks of the organism in health care facilities have 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 nonaggregative (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, while treatment alone was nontoxic 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.

Filling the Void: An Optimized Polymicrobial Interkingdom Biofilm Model for Assessing Novel Antimicrobial Agents in Endodontic Infection

“…Results indicated that following treatment with chitosan, there were significant reductions in the total CFE/mL of the mixed-species biofilms ( Figure 6 A; **** p < 0.0001), which was in agreement with the results described in Figure 5 . The compositional changes of the biofilm ( Figure 6 B,C, and Table 4 ) indicated that the treatment reduced the levels of C. albicans from ~14.51% to ~3.48%, which is in line with previous publications that chitosan possesses antifungal activity [ 27 , 28 , 29 , 30 , 31 ]. Results from this and preceding sections indicate that chitosan may be an effective alternative to conventional endodontic therapeutics.…”

“…The compound is known to possess antimicrobial activity against a variety of bacteria (both Gram-positive and Gram-negative) and fungi [ 30 , 51 ]. Further to this, recently our group has shown that chitosan is effective against the nosocomial pathogens C. albicans and C. auris , both in vitro and in vivo [ 31 , 52 ]. The potential use of chitosan in endodontic treatment is not unheard of, with a recent publication highlighting that chitosan nanoparticles, when incorporated into a paste with propolis, an extract from honey, was effective in reducing the colony forming units of an E. faecalis biofilm grown on human root canal dentin [ 53 ].…”

Virulence ofCandida aurisfrom different clinical origins inCaenorhabditis elegansandGalleria mellonellahost models

“…Advances in the knowledge of the virulence potential of C. auris will contribute to the control of infections by this emerging pathogen. Recently, two different phenotypes, aggregating and non-aggregating (single-cell phenotype), have been described among C. auris clinical isolates; the latter presenting a higher virulence [ 21 , 22 , 26 ]. Transcriptional profiles were evidently different between isolates with these two different phenotypes, and differences in the host response, depending on whether there is loss of tissue integrity, were also reported [ 12 ].…”

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

“…In a galleria mellonella model of C. auris infection, chitosan decreased the killing effects of C. auris infection without any toxicity to the larvae. The putative mode of action of chitosan could be mediated by the expression of a stress-like gene expression response, conducting to protection in the larvae [ 127 ].…”