A brand new study has found that a natural compound present in many plants inhibits the expansion of drug-resistant fungi — including a few of its most virulent species, an emerging global health threat. Is. The journal published the invention led by scientists at Emory University.
Laboratory dish experiments showed that a natural compound, a water-soluble tannin called PGG, inhibited the expansion of 4 various kinds of fungi by 90 percent. The researchers also discovered how PGG inhibits growth: It traps iron molecules, essentially ravenous the fungus of a vital nutrient.
By ravenous the fungus as a substitute of attacking it, the PGG mechanism doesn't promote further drug resistance, unlike current antifungal drugs. Laboratory dish experiments also showed minimal toxicity of PGG to human cells.
“Drug-resistant fungal infections are a growing health care problem, but the drug development pipeline has been growing,” says Cassandra Cove, senior writer of the study and assistant professor within the Department of Dermatology and Cardiology Center at Emory School of Medicine. There are some recent antifungals within the line.” Human health studies. “Our findings open up a brand new potential approach to combating these infections, including those brought on by malignancy.”
It is usually multidrug-resistant and has a high mortality rate, leading the Centers for Disease Control and Prevention (CDC) to designate it a serious global health threat.
“It's a really bad bug,” says Lewis Marquez, first writer of the study and a graduate student in Emory's Molecular Systems and Pharmacology program. “Between 30 and 60% of those infected die.”
Emerging threat
is a yeast that is usually found on the skin and within the digestive tract of healthy people. Some species, eg, occasionally get uncontrolled and cause mild infections in people.
In more severe cases, it may invade deeper into the body and cause infection within the bloodstream or in organs resembling the kidneys, heart, or brain. Immunocompromised people, including many hospital patients, are at best risk for invasive infections, that are increasingly developing drug resistance.
In 2007, the brand new strain emerged in a hospital patient in Japan. Since then, healthcare-associated outbreaks have occurred in greater than a dozen countries worldwide, and greater than 3,000 clinical cases have been reported within the United States alone.
A 'naturalistic' approach to drug discovery
Quave is an ethnologist, studying how traditional peoples have used plants for medicine with a view to find recent candidates for contemporary medicine. His laboratory produces the Quave Natural Product Library, which comprises 2,500 botanical and fungal natural products from 750 species collected at sites around the globe.
“We're not taking a random approach to identifying potential new antimicrobials,” says Quave. “Focusing on plants used in traditional medicine allows us to quickly work on bioactive molecules.”
Earlier, the Quave lab found that the berries of Brazilian peppertree, a plant that has been used for hundreds of years by traditional healers within the Amazon to treat skin infections and another ailments, contain flavone-rich compounds. occurs that disarms drug-resistant staph bacteria.
Quave lab screens also revealed that Brazilian peppertree leaves contain PGG, a compound that has shown antibacterial, anticancer and antiviral activity in previous research.
A 2020 study by the Quave Lab, for instance, found that PGG inhibited the event of carbapenem resistance, a bacterium that infects humans and is listed as one among the five most urgent threats by the CDC. Rated at
Brazilian peppertree, an invasive weed in Florida, is a member of the poison ivy family. “PGG has popped up repeatedly in our laboratory screens of plant compounds from members of this plant family,” says Quave. “It makes sense that these plants, which thrive in really wet environments, have molecules to fight off a wide variety of pathogens.”
Experimental results
Quave Lab decided to check whether PGG would show antifungal activity.
Laboratory dish experiments demonstrated that PGG inhibited roughly 90% of growth in 12 strains of which 4 were: multidrug-resistant and two other multidrug-resistant non-albicans species.
PGG is a big molecule known for its iron-binding properties. The researchers tested the role of this feature in antifungal activity.
“Each PGG molecule can bind five iron molecules,” explains Marquez. “When we added more iron to a dish, beyond the ability of the PGG molecules to sequester, the fungus once again grew normally.”
Dish experiments also showed that PGG was well tolerated by human kidney, liver and epithelial cells.
“Iron in human cells is not usually free iron,” Marquez says. “It's usually bound to a protein or sequestered within enzymes.”
Treatment of possible conditions
Previous animal studies on PGG have shown that the molecule is rapidly metabolized and eliminated from the body. Instead of internal therapy, researchers are testing its potential efficacy as a topical antifungal.
“If a patient develops an infection on the skin where a catheter or other medical device is inserted, a topical antifungal can prevent the infection from spreading and entering the body,” says Marquez.
As a next step, the researchers will test PGG as a topical treatment for fungal skin infections in mice.
Meanwhile, Quave and Marquez have applied for a provisional patent for using PGG to eradicate fungal infections.
“It's still early days of research, but another idea we're interested in pursuing is the potential use of PGG as a broad-spectrum microbial,” says Quave. “Many infections from acute wounds, such as battlefield wounds, are polymicrobial so PGG may be a useful topical treatment in these cases.”
University of Toronto scientists co-authored the paper, including Yunjin Li, Dustin Duncan, Luke Whitsell and Leah Kwon. Whitesell and Cowen are co-founders and shareholders in BrightAngel Therapeutics, a platform company for the event of antifungal therapies, and Cowen is a science advisor to KapuzCreek, an organization that exploits the therapeutic potential of fungi. brings
This work was supported by grants from the National Institutes of Health, National Center for Complementary and Integrative Health. The Jones Center at Ichauway, the CIHR Frederick Banting and Charles Best Canada Graduate Scholarship and the Canadian Institutes of Health Research Foundation.