https://orcid.org/0000-0002-9141-9717
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Abstract
Purpose
The resistance of C. albicans to traditional antifungal drugs brings a great challenge to clinical treatment. To overcome the resistance, developing antifungal agent sensitizers has attracted considerable attention. This study aimed to determine the anti-Candida activity of BEH alone or BEH–FLC combination and to explore the underlying mechanisms.
Materials and Methods
In vitro antifungal effects were performed by broth microdilution assay and XTT reduction assay. Infected Galleria mellonella larvae model was used to determine the antifungal effects in vivo. Probes Fluo-3/AM, FITC-VAD-FMK and rhodamine 6G were used to study the influence of BEH and FLC on intracellular calcium concentration, metacaspase activity and drug efflux of C. albicans.
Results
BEH alone exhibited obvious antifungal activities against C. albicans. BEH plus FLC not only showed synergistic effects against planktonic cells and preformed biofilms within 8 h but also enhanced the antifungal activity in infected G. mellonella larvae. Mechanistic studies indicated that antifungal effects of drugs might be associated with the increasement of calcium concentration, activation of metacaspase activity to reduce virulence and anti-biofilms, but were not related to drug efflux.
Conclusion
BEH alone or combined with FLC displayed potent antifungal activity both in vitro and in vivo, and the underlying mechanisms were related to reduced virulence factors.
Acknowledgments
We would like to thank the grants from the Beijing Health Alliance Charitable Foundation (WS630A).
Ethical Approval
The animal models used in this study are G. mellonella larvae, which do not require ethical approval.
Disclosure
The authors report a patent ZL202010782426.2 licensed to Shujuan Sun; Xueqi Chen; Chunyan Li; Haiying Yan; Hongyao Ren. The authors report no other conflicts of interest in this work.