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New hope in deadly fungal infections

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Candida albicans (Callie Jones)Part of the normal human flora is Candida albicans, a well known fungus that exists, in the form of yeast cells, predominantly on mucocutaneous surfaces such as the mouth, gastrointestinal tract and vaginal cavity. In conditions favourable to it, it can present as an opportunistic pathogen, producing symptoms of oral and genital thrush.

It is, however, polymorphic, and under certain conditions can undergo transition to a hyphal form. Over recent decades, fungal infections have become important hospital-acquired infections, owing to the increasing number of immunocompromised patients, and those in hospital with conditions such as cancer, after organ transplantation or in neonatal units.

The ability of C albicans to convert from the yeast state is critical for systemic infections, because the hyphal cells penetrate and adhere to the tissues, where they are protected from the host’s phagocytes and difficult to treat with antifungal agents. They are able to aggregate into layers known as biofilms, which render them even more resistant, and the death rate from invasive candidiasis is high.

A research team from the University of Kansas recently screened extracts from more than 50 plants with a long history of safe use as herbal medicines, to test for natural antifungal compounds (C albicans is also a plant pathogen in the hyphal form).

One group of triterpenoid saponins extracted from the tropical Asian vine Gymnema sylvestre, known as gymnemic acids, showed remarkable activity not only as potent inhibitors of the conversion of C albicans from the yeast to the hyphal form, but also in triggering conversion of the hyphal forms back to yeast. They also demonstrated effectiveness in the penetration and conversion of biofilms back to yeast cells.

The gymnemic acids are not lethal to C albicans but, by inhibiting the hyphal phase and returning it to the yeast state, they allow treatment with conventional antifungal drugs.

Further research demonstrated activity also against the pathogen aspergillus, which is notoriously difficult to treat. It is hoped that gymnemic acids can be used as templates for future antifungal drug development.

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From: Beyond pharmacy blog

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