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

• Type of Material: Article
• Authors: lewis marquez, Emory University; Yunjin Lee, University of Toronto; Dustin Duncan, University of Toronto; Luke Whitesell, University of Toronto; Leah E. Cowen, University of Toronto; Cassandra Leah Quave, Emory University
• Language: English
• Date: 2023-08-22
• Publisher: American Chemical Society
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Published by American Chemical Society
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1021%2Facsinfecdis.3c00113
• Title of Journal or Parent Work: American Chemical Society Infectious Diseases
• Volume: 9
• Issue: 9
• Start Page: 1685
• End Page: 1694
• Grant/Funding Information: This work was supported in part by a grant from the National Institutes of Health, National Center for Complementary and Integrative Health (NCCIH) (R01AT011990 to C.L.Q.) and a graduate student fellowship from The Jones Center at Ichauway to L.M. Y.L. is supported by the CIHR Frederick Banting and Charles Best Canada Graduate Scholarship—Doctoral Awards.
• Keywords: mechanism of action; candidiasis; natural product; iron chelation
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

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 IC50 > 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.