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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 results indicated that chitosan was effective against planktonic and sessile forms of Agg and non-Agg 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 virulence, chitosan treatment was shown to ameliorate killing effects of both C. auris virulence, chitosan treatment was shown to ameliorate killing effects of both C. auris Specifically, chitosan reduced the fungal load and increased survival rates of infected in vivo , 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 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 ., (Copyright © 2020 American Society for Microbiology.)

This study synthesized and characterized a chlorhexidine (CHX)-carrier nanosystem based on iron oxide magnetic nanoparticles (IONPs) and chitosan (CS), and evaluated its antimicrobial effect on mono- and dual-species biofilms of Candida albicans and Streptococcus mutans. CHX was directly solubilized in CS-coated IONPs and maintained under magnetic stirring for obtaining the IONPs-CS-CHX nanosystem. Antimicrobial susceptibility testing for planktonic cells was performed by determining the minimum inhibitory concentration (MIC) of the nanosystem and controls. The effects of the IONPs-CS-CHX nanosystem on the formation of mono- and dual-species biofilms, as well as on pre-formed biofilms were assessed by quantification of total biomass, metabolic activity and colony-forming units. Data were analyzed by the Kruskal-Wallis' test or one-way analysis of variance, followed by the Student-Newman-Keuls' or Holm-Sidak's tests (α = 0.05), respectively. Physico-chemical results confirmed the formation of a nanosystem with a size smaller than 40 nm. The IONPs-CS-CHX nanosystem and free CHX showed similar MIC values for both species analyzed. In general, biofilm quantification assays revealed that the CHX nanosystem at 78 μg/mL promoted similar or superior antibiofilm effects compared to its counterpart at 39 μg/mL and free CHX at 78 μg/mL. These findings highlight the potential of CS-coated IONPs as preventive or therapeutic agents carrying CHX to fight biofilm-associated oral diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The contribution of different Candida species in oral fungal infections has stimulated the search for more effective therapies. This study assessed the antibiofilm effects of nanocarriers of miconazole (MCZ) or fluconazole (FLZ) on Candida biofilms, and their cytotoxic effects on murine fibroblasts. Three-species biofilms (Candida albicans/Candida glabrata/Candida tropicalis) were formed on 96-well plates, and they were treated with nanocarriers (iron oxide nanoparticles coated with chitosan-"IONPs-CS") of MCZ or FLZ at 39/78/156 µg/mL; antifungals alone at 156 µg/mL and artificial saliva were tested as positive and negative controls, respectively. Biofilms were analyzed by colony forming units (CFU), biomass, metabolic activity, and structure/viability. The cytotoxicity (L929 cells) of all treatments was determined via 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Data were submitted to one- or two-way ANOVA, followed by Tukey's or Fisher LSD's tests (p < 0.05). IONPs-CS-MCZ at 78 µg/mL promoted similar antibiofilm and cytotoxic effects compared with MCZ at 156 µg/mL. In turn, IONPs-CS-FLZ at 156 µg/mL was overall the most effective FLZ antibiofilm treatment, surpassing the effects of FLZ alone; this nanocarrier was also less cytotoxic compared with FLZ alone. It can be concluded that both nanocarriers are more effective alternatives to fight Candida biofilms compared with their respective positive controls in vitro, being a promising alternative for the treatment of oral fungal infections. [ABSTRACT FROM AUTHOR]

• A nanocarrier of miconazole has been successfully assembled. • The nanocarrier was more effective on Candida planktonic cells than miconazole. • The nanocarrier showed superior antibiofilm effect to miconazole alone. • The nanocarrier acts at the cellular level, not affecting the biofilms' matrix. • The use of magnetic field did not affect the antibiofilm effect of the nanocarrier. Overexposure of microorganisms to conventional drugs has led to resistant species that require new treatment strategies. This study prepared and characterized a nanocarrier of miconazole (MCZ) based on iron oxide nanoparticles (IONPs) functionalized with chitosan (CS), and tested its antifungal activity against biofilms of Candida albicans and Candida glabrata. IONPs-CS-MCZ nanocarrier was prepared by loading MCZ on CS-covered IONPs and characterized by physicochemical methods. Minimum inhibitory concentration (MIC) of the nanocarrier was determined by the microdilution method. Biofilms were developed (48 h) in microtiter plates and treated with MCZ-carrying nanocarrier at 31.2 and 78 μg/mL, in both the presence and absence of an external magnetic field (EMF). Biofilms were evaluated by total biomass, metabolic activity, cultivable cells (CFU), extracellular matrix components, scanning electron microscopy and confocal microscopy. Data were analyzed by two-way ANOVA and Holm-Sidak test (p < 0.05). A nanocarrier with diameter lower than 50 nm was obtained, presenting MIC values lower than those found for MCZ, and showing synergism for C. albicans and indifference for C. glabrata (fractional inhibitory concentration indexes of <0.12 and <0.53, respectively). IONPs-CS-MCZ did not affect total biomass and extracellular matrix. IONPs-CS-MCZ containing 78 μg/mL MCZ showed a superior antibiofilm effect to MCZ in reducing CFU and metabolism for single biofilms of C. albicans and dual-species biofilms. The EMF did not improve the nanocarrier effects. Microscopy confirmed the antibiofilm effect of the nanocarrier. In conclusion, IONPs-CS-MCZ was more effective than MCZ mainly against C. albicans planktonic cells and number of CFU and metabolism of the biofilms. [ABSTRACT FROM AUTHOR]