New class of anti-fungal drugs discovered

A new class of anti-fungals to treat people suffering from serious fungal infections has been found, new research says.

Fungal infections are most commonly found in individuals with medical conditions that compromise the immune system like AIDS, or individuals who are battling cancer.

"Fungal infections are a significant cause of morbidity and mortality worldwide and current anti-fungal drugs have drawbacks. These new drugs may pave the way for the development of a new class of anti-fungals," said principal investigator Maurizio Del Poeta, professor in the department of molecular genetics and microbiology at Stony Brook University, New York.

The three classes of anti-fungal drugs currently available - azoles, polyenes, and echinocandins - don't work that well. They are toxic, so they affect other organs, and they are static, meaning they may be able to stop a fungus from replicating but they are not able to kill the fungus.

When fungal cells lack a lipid called glucosylceramide (GlcCer), they are unable to replicate. Taking a cue from this weakness and develop a new class of anti-fungals, the team screened a synthetic drug library for compounds that target the synthesis of fungal but not mammalian GlcCer.

"The enzymes that are important for the synthesis of fungal glucosylceramide are different than the ones important for the synthesis of mammalian glucosylceramide," Del Poeta said.

They identified two compounds, BHBM and its derivative DO, that decreased levels of fungal but not mammalian glucosylceramide.

In test tube and animal studies, these compounds were highly effective against several pathogenic fungi and were well tolerated in animals.

The drugs were effective when used alone or in combination with other classes of anti-fungals. Serious fungal infections cause 1.3 million deaths annually worldwide.

The most common and life-threatening fungal infections are cryptococcosis, candidiasis, aspergillosis, and pneumocystosis.

The research was outlined in the current issue of the journal mBio.