Fighting Drug-Resistant Fungal Infections with Natural Solutions

Our latest publication reveals groundbreaking findings on penta-O-galloyl-β-d-glucose (PGG) as a potent weapon against multidrug-resistant Candida species.

Aug 29, 2023

We have a new research publication resulting from a collaboration between the Quave Lab at Emory University and the Cowen lab at The University of Toronto! The research findings were published in the American Chemical Society journal ACS Infectious Diseases.

The publication is available through an open access model and you can read it in full by clicking on the title link:

Marquez, L., Y. Lee, D. Duncan, L. Whitesell, L.E. Cowen, C. Quave. Potent Antifungal Activity of Penta-O-galloyl-β-d-Glucose against Drug-Resistant Candida albicans, Candida auris, and Other Non-albicans Candida Species. ACS Infectious Diseases, https://doi.org/10.1021/acsinfecdis.3c00113

This research was supported with funding from the National Institutes of Health National Center for Complementary and Integrative Health, The Jones Center at Ichauway, CIHR Frederick Banting and Charles Best Canada Graduate Scholarship, Canadian Institutes of Health Research Foundation, and philanthropic donations to the Quave Lab. Here, I break down some of the major findings from the research project.

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The Challenge of Candida Infections

Candida is a common yeast that usually lives harmlessly in areas like your gut or on your skin. However, in some cases, it can lead to skin infections or even more severe issues if it gets into your bloodstream or major organs. In the U.S., around 25,000 people deal with serious Candida infections each year. Alarmingly, a new type of Candida called Candida auris has emerged, which is even more deadly and has been spreading across multiple states. One major challenge is that these Candida strains are becoming resistant to existing antifungal drugs, making them harder to treat.

There are ~25,000 serious Candida infections in the USA each year.
Invasive (infections in the blood and organs) Candida infections have a mortality (death) rate of 29-31% in USA patients. In South Africa and Brazil, mortality rates have reached 60% and 72%, respectively.

The Active Compound: PGG

Chemical structure of penta-O-galloyl-β-d-glucose, PGG.

Due to increasing drug resistance and a lack of new antifungals, the need for alternative treatments for Candida infections has become urgent. Our team turned to traditional remedies and found that the Brazilian peppertree, known for its antiseptic properties, could offer a solution. We initially isolated a compound called penta-O-galloyl-β-d-glucose (PGG) from the tree's leaves. We then used a commercial source of the molecule for our subsequent studies.

Other researchers have reported on PGG’s multiple beneficial effects, including antibacterial, anticancer, and antiviral activities. In our study, PGG showed promising results in inhibiting the growth of various drug-resistant Candida strains, leading us to further investigate how it works as an antifungal.

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Major Findings

Our study reveals that PGG exhibits strong antifungal activity against multiple strains of Candida species, including highly drug resistant strains. PGG was found to be as effective, or even more so, than conventional antifungal drugs when tested in standard conditions. Notably, PGG displayed low cytotoxicity against human kidney, liver, and skin cells. However, its effectiveness reduced significantly when we tested it in the presence of fetal bovine serum, suggesting that some components in the serum might interfere with its action. Despite this, other studies have shown that PGG can be safely administered in both animals and humans, indicating that the compound is generally well-tolerated. One major drawback is that PGG breaks down quickly in the body, making it a poor candidate for systemic treatment but potentially useful for topical applications.

Strengths of PGG as an Antifungal Drug:

Potent antifungal activity against multiple strains of Candida species, including the CDC-ranked “Urgent Threat” pathogen, Candida auris.
Low cytotoxicity in human cells, suggesting safety for potential therapeutic use.
Mechanism of action involves iron chelation, a strategy proven effective in other antifungals like ciclopirox.
Resistance to PGG may be less likely to develop due to its iron-chelating mechanism.

Importantly, PGG is superior to ciclopirox in its iron-binding capacity─three molecules of ciclopirox bind one iron ion, whereas we found one molecule of PGG binds up to five iron ions!

Weaknesses of PGG as an Antifungal Drug:

Loss of effectiveness in the presence of certain biological components like fetal bovine serum.
High clearance rate and rapid breakdown in the body, making it likely unsuitable for systemic treatment.
Unknown long-term effects and potential for negative interactions with other medications or conditions.

The Takeaway

The evidence suggests that despite its potential weaknesses for systemic use, PGG's strong antifungal and iron-chelating abilities make it a promising candidate for topical treatments against Candida skin infections. Furthermore, this study is yet another example of how investigation of traditional remedies used in the treatment of infectious and inflammatory diseases can reveal exciting new findings on molecules that could be developed into new, lifesaving, medications.

If you would like to support more research like this, please consider a philanthropic donation to the Quave Lab at Emory University. Donations are tax-deductible and can be made on this dedicated Emory Giving page, which ensures all donations go directly to supporting research in my lab. In addition to cash donations, Emory can facilitate gifts of stocks, real estate, or planned giving in estate planning. More information is available at the main Emory Giving website.

Yours in health, Dr. Quave