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

Abstract

High Resolution Image Download MS PowerPoint Slide 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.