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

Among fungal pathogens, infections by drug-resistant Candida species continue to pose a major challenge to healthcare.This studyaimed to evaluate the activity of the bioactive natural product, penta-O-galloyl-& beta;-d-glucose (PGG) against multidrug-resistant(MDR) Candida albicans, MDR Candida auris, and other MDR non-albicansCandida species. Here, we show that PGG has a minimum inhibitoryconcentration (MIC) of 0.25-8 & mu;g mL(-1) (0.265-8.5 & mu;M) against three clinical strains of C. auris and a MIC of 0.25-4 & mu;g mL(-1) (0.265-4.25 & mu;M) against a panel of otherMDR Candida species. Our cytotoxicity studies foundthat PGG was well tolerated by human kidney, liver, and epithelialcells with an IC50 > 256 & mu;g mL(-1) (>272 & mu;M). We also show that PGG is a high-capacity ironchelatorand that deletion of key iron homeostasis genes in C. albicans rendered strains hypersensitive to PGG.In conclusion, PGG displayed potent anti-Candida activitywith minimal cytotoxicity for human cells. We also found that theantifungal activity of PGG is mediated through an iron-chelating mechanism,suggesting that the compound could prove useful as a topical treatmentfor superficial Candida infections.