HEALTH NEWS

Study Title:

Gymnemic Acids Inhibit Hyphal Growth and Virulence in Candida albicans

Study Abstract

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine.

From press release:

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 mortality rates for those with candidemia and invasive candidiasis has been reported to be quite high, 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.

Study Information

Govindsamy Vediyappan, Vincent Dumontet, Franck Pelissier, Christophe d’Enfert
Gymnemic Acids Inhibit Hyphal Growth and Virulence in Candida albicans
PLoS ONE
2013 September
Kansas State University