Drug-Resistance: Extract from Chestnut Leaves Disarms Staph

In a one-two punch, European chestnut tree leaves contain derivatives that block the commonly known staph bacteria without increasing its drug resistance, scientists have found. 

Cassandra Quave and colleagues at Emory learned that the chestnut leaves contain ursene and oleanene derivatives after they researched traditional remedies of rural people in Southern Italy and other parts of the Mediterranean. Their research is to be published in the journal, PLOS ONE. 

"We've identified a family of compounds from this plant that have an interesting medicinal mechanism," Quave said in a statement. "Rather than killing staph, this botanical extract works by taking away staph's weapons, essentially shutting off the ability of the bacteria to create toxins that cause tissue damage. In other words, it takes the teeth out of the bacteria's bite."

This holds the potential for methicillin-resistant Staphlococcus aureus, or MRSA, caused by one strain of staph, to be treated and prevented without increasing drug-resistant pathogens. Those resistant to antibiotics generally cause at least two million illnesses and 23,000 deaths in the United States annually, according to the Centers for Disease Control and Prevention. Staph infections can lead to everything from mild skin irritations to fatalities, since strains of this bacteria are able to evolve. So everyone from hospital patients with compromised immune systems, to young healthy athletes, are threatened if in close contact with those infected.

"We've demonstrated in the lab that our extract disarms even the hyper-virulent MRSA strains capable of causing serious infections in healthy athletes," Quave, an ethnobotanist, said in the release. "At the same time, the extract doesn't disturb the normal, healthy bacteria on human skin. It's all about restoring balance."

"I felt strongly that people who dismissed traditional healing plants as medicine because the plants don't kill a pathogen were not asking the right questions," she explained in the release. "What if these plants play some other role in fighting a disease?"

For this study, Quave, along with Alexander Horswill, a microbiologist at the University of Iowa, soaked chestnut leaves in solvents to extract their chemical ingredients.

"You separate the complex mixture of chemicals found in the extract into smaller batches with fewer chemical ingredients, test the results, and keep honing in on the ingredients that are the most active," Quave said in the release. "It's a methodical process and takes a lot of hours at the bench. Emory undergraduates did much of the work to gain experience in chemical separation techniques."

From this process, the team was able to produce an extract of 94 chemicals, of which ursene and oleanene based compounds are the most active. They then discovered that this extract inhibits the ability of staph bacteria to communicate with one another, a process known as quorum sensing, which MRSA uses to manufacture toxins and increase its virulence.

"We were able to trace out the pathways in the lab, showing how our botanical extract blocks quorum sensing and turns off toxin production entirely," Quave said. "Many pharmaceutical companies are working on the development of monoclonal antibodies that target just one toxin. This is more exciting because we've shown that with this extract, we can turn off an entire cascade responsible for producing a variety of different toxins."

According to their study, a single dose of the extract -- about 50 micrograms -- was able to clear up MRSA skin lesions in lab mice, and stopped tissue damage and red blood cell damage. They also found that this extract didn't lose activity, or become resistant, even after two weeks of repeated exposure. Further tests on human skin cells in a lab dish showed that the botanical extract does not harm the skin cells, or the normal skin micro-flora. However, more testing needs to be conducted on the individual components of the extract to determine if they work best in combination or alone.

"We now have a mixture that works," Quave says. "Our goal is to further refine it into a simpler compound that would be eligible for FDA consideration as a therapeutic agent."

Meanwhile, the Emory Office of Technology Transfer has filed a patent for the researchers' discovery. Uses of this unique botanical extract range from spray for football pads to potential combination with antibiotics.

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