Potent Antifungal Activity of Penta-O-galloyl-β-d-Glucose against Drug-Resistant Candida albicans, Candida auris, and Other Non-albicans Candida Species

[Image: see text] Among fungal pathogens, infections by drug-resistant Candida species continue to pose a major challenge to healthcare. This study aimed to evaluate the activity of the bioactive natural product, penta-O-galloyl-β-d-glucose (PGG) against multidrug-resistant (MDR) Candida albicans, MDR Candida auris, and other MDR non-albicans Candida species. Here, we show that PGG has a minimum inhibitory concentration (MIC) of 0.25–8 μg mL(–1) (0.265–8.5 μM) against three clinical strains of C. auris and a MIC of 0.25–4 μg mL(–1) (0.265–4.25 μM) against a panel of other MDR Candida species. Our cytotoxicity studies found that PGG was well tolerated by human kidney, liver, and epithelial cells with an IC(50) > 256 μg mL(–1) (>272 μM). We also show that PGG is a high-capacity iron chelator and that deletion of key iron homeostasis genes in C. albicans rendered strains hypersensitive to PGG. In conclusion, PGG displayed potent anti-Candida activity with minimal cytotoxicity for human cells. We also found that the antifungal activity of PGG is mediated through an iron-chelating mechanism, suggesting that the compound could prove useful as a topical treatment for superficial Candida infections.