CHESTNUT LEAVES YIELD EXTRACT THAT DISARMS DEADLY STAPH BACTERIA
Leaves of the European chestnut tree contain
ingredients with the power to disarm dangerous staph bacteria without boosting
its drug resistance, scientists have found
PLOS
ONE is publishing the study of a
chestnut leaf extract, rich in ursene and oleanene derivatives, that blocks Staphlococcus
aureus virulence and pathogenesis without detectable resistance.
The
use of chestnut leaves in traditional folk remedies inspired the research, led
by Cassandra Quave, an ethnobotanist at Emory University.
"We've
identified a family of compounds from this plant that have an interesting
medicinal mechanism," Quave says. "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."
The
discovery holds potential for new ways to both treat and prevent infections of
methicillin-resistant S. aureus, or MRSA, without fueling the
growing problem of drug-resistant pathogens.
Antibiotic-resistant
bacteria annually cause at least two million illnesses and 23,000 deaths in the
United States, according to the Centers for Disease Control and Prevention.
MRSA infections lead to everything from mild skin irritations to fatalities.
Evolving strains of this "super bug" bacterium pose threats to both
hospital patients with compromised immune systems and young, healthy athletes
and others who are in close physical contact.
"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
says. "At the same time, the extract doesn't disturb the normal, healthy
bacteria on human skin. It's all about restoring balance."
Quave,
who researches the interactions of people and plants -- a specialty known as
ethnobotany -- is on the faculty of Emory's Center for the Study of Human
Health and Emory School of Medicine's Department of Dermatology. She became
interested in ethnobotany as an undergraduate at Emory.
For
years, she and her colleagues have researched the traditional remedies of rural
people in Southern Italy and other parts of the Mediterranean. "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 says. "What if these plants play some other role in
fighting a disease?"
Hundreds
of field interviews guided her to the European chestnut tree, Castanea sativa.
"Local people and healers repeatedly told us how they would make a tea
from the leaves of the chestnut tree and wash their skin with it to treat skin
infections and inflammations," Quave says.
For
the current study, Quave teamed up with Alexander Horswill, a microbiologist at
the University of Iowa whose lab focuses on creating tools for use in drug
discovery, such as glow-in-the-dark staph strains.
The
researchers steeped 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
explains. "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."
The
work produced an extract of 94 chemicals, of which ursene and oleanene based
compounds are the most active.
Tests
showed that this extract inhibits the ability of staph bacteria to communicate
with one another, a process known as quorum sensing. MRSA uses this
quorum-sensing signaling system to manufacture toxins and ramp up 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 says. "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."
A
single dose of the extract, at 50 micrograms, cleared up MRSA skin lesions in
lab mice, stopping tissue damage and red blood cell damage. The extract does
not lose activity, or become resistant, even after two weeks of repeated
exposure. And 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.
The
Emory Office of Technology Transfer has filed a patent for the discovery of the
unique properties of the botanical extract. The researchers are doing further
testing on 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."
Potential
uses include a preventative spray for football pads or other athletic
equipment; preventative coatings for medical devices and products such as
tampons that offer favorable environments for the growth of MRSA; and as a
treatment for MRSA infections, perhaps in combination with antibiotics.
"It's
easy to dismiss traditional remedies as old wives' tales, just because they
don't attack and kill pathogens," Quave says. "But there are many
more ways to help cure infections, and we need to focus on them in the era of
drug-resistant bacteria."
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