A Kansas State University microbiologist has found a
breakthrough herbal medicine treatment for a common human fungal
pathogen that lives in almost 80 percent of people.
Govindsamy Vediyappan,
assistant professor of biology, noticed that diabetic people in
developing countries use a medicinal herb called Gymnema slyvestre to
help control sugar levels. He decided to study the microbiological use
of Gymnema slyvestre -- a tropical vine plant found in India, China and
Australia -- to see if it could treat a common human fungal pathogen
called Candida albicans.
The investigation was
successful on two levels: Vediyappan's research team found the medicinal
compound is both nontoxic and blocks the virulence properties of the
fungus so that it is more treatable. The results are important for human
health, biomedical applications and potential drug development.
"We
have shown that this compound is safe to use because it doesn't hurt
our body cells, yet it blocks the virulence of this fungus under in
vitro conditions," Vediyappan said. "Taking the medicine could
potentially help patients control the invasive growth of the fungus and
also help bring their sugar levels down."
Candida
albicans is one of the major fungal pathogens in humans because it lives
in oral and intestinal areas as a normal flora, Vediyappan said. But
the fungus can overgrow and can cause oral, intestinal and genital
infections. The fungus kills almost 30 percent of people who have it and
it is a concern among cancer patients -- especially patients with neck
or oral cancer -- HIV patients, organ transplant patients and other
people with compromised immune systems.
The fungus
can grow in two forms: a treatable yeast and a difficult-to-treat hyphal
form. Once the fungus transforms from a yeast to a hyphal growth it
becomes difficult to treat because the hyphal growth has long
filament-like structures that can spread into various organs.
Vediyappan's study aimed to block the hyphal growth form.
"Once it gets into the tissue, it spreads like roots and is difficult to contain by our immune system," Vediyappan said.
If
the fungus remains in yeast form, it is easy to manage and does not
invade tissues. Vediyappan's research team purified gymnemic acid
compounds that prevented the transition stage from occurring and stopped
the fungus spread. The gymnemic acids come from the leaves of Gymnema
sylvestre, a traditional medicinal plant.
The research appears in the peer-reviewed journal PLOS ONE in an article titled “Gymnemic acids inhibit hyphal growth and virulence in Candida albicans."
Gymnema
extract is commonly used to treat diabetes and other ailments because
it is a cost-effective treatment, Vediyappan said. Often, people drink
the extract to control their sugar levels or to lose weight.
Although
Vediyappan's research team is not the first to discover gymnemic acid
compounds, the team is the first to discover that the compounds block
the fungal transition. The researchers found that the compounds work
quickly, too, which was an important characteristic. The treatable
fungal yeast can transition to a hyphal growth within 30 minutes of an
infection. When the hyphal transition has occurred, it will grow into
branched filaments.
The gymnemic acid compounds are
nontoxic, which is especially important for cancer patients and other
immunocompromised patients. The gymnemic acids can stop the unwanted
invasive infection while preserving important healthy cells.
The
Candida albicans fungus also makes a biofilm, which is a fungal cell
collection that can be difficult to treat. The researchers found that
the gymnemic acid compounds converted the biofilm back to treatable
yeast cells.
"This compound prevents the biofilm
formation because hyphae are the major builders of biofilms and biofilms
are resistant to antifungals," Vediyappan said. "Yeast cells by
themselves cannot make biofilms and are sensitive to antifungal
treatments."
Another interesting aspect: The
gymnemic acid compounds also stopped the growth of Aspergillus, another
fungal pathogen that can affect heart transplant patients and leukemia
patients.
Vediyappan plans future studies to
research mode of action, potential drug development, diabetes
applications and other ways to improve treatment for Candida albicans
and other fungal pathogens.
Funding for the research came from Kansas State University's Johnson Cancer Research Center
and K-INBRE at the University of Kansas Medical Center. Collaborating
researchers include Vincent Dumontet and Franck Pelissier with the
Natural Product Chemistry Institute, part of the National Center for
Scientific Research, in Gif-sur-Yvette, France; and Christophe d'Enfert
with the Fungal Biology and Pathogenicity Unit in the Department of
Genomes and Genetics at the Institut Pasteur in Paris, France.
Source:Kansas State University
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