Researchers identify new class of antifungal agents

June 23, 2015, American Society for Microbiology

Researchers have identified a new class of antifungals to treat the more than 300 million people worldwide who develop serious fungal infections. The research is described in the current issue of mBio, the online open-access journal of the American Society for Microbiology.

"Fungal infections are a significant cause of morbidity and mortality worldwide and current antifungal drugs have drawbacks. These may pave the way for the development of a new class of ," said principal investigator Maurizio Del Poeta, MD, a professor in the Department of Molecular Genetics and Microbiology at Stony Brook University, Stony Brook, New York.

Fungal infections are most commonly found in individuals with medical conditions that compromise the immune system, such as AIDS, or individuals who are being treated with immunosuppressives, such as those battling cancer. The three classes of currently available—azoles, polyenes, and echinocandins—are far from optimal.

"Even with treatment, the mortality rate of invasive is over 50%," said Dr. Del Poeta. "The drugs 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." Current antifungals also have a narrow spectrum of activity, and some interact with other drugs such as chemotherapy agents and immunosuppressants."

Previous research has shown that when fungal cells lack a lipid called glucosylceramide (GlcCer), they are unable to replicate. Seeking to exploit this weakness and develop a new class of antifungals, an international group of researchers screened a synthetic 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," said Dr. Del Poeta. "We thought that because the pathway is totally different, we could specifically target the fungal glucosylceramide without affecting mammalian glucosylceramide, and that is exactly what we did."

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 antifungals. The researchers plan to spend the next five years fine-tuning their research and identifying even more effective compounds that inhibit fungal glucosylceramide.

Serious fungal infections cause 1.3 million deaths annually worldwide. The most common and life-threatening fungal infections are cryptococcosis, candidiasis, aspergillosis, and pneumocystosis.

Explore further: Company reports antifungal compounds that evade resistance

More information: mbio.asm.org/content/6/3/e00647-15

Related Stories

Company reports antifungal compounds that evade resistance

June 1, 2015

REVOLUTION Medicines, Inc., a company focused on the discovery and development of innovative drugs derived from natural compounds, announced that progress in antimicrobial drug discovery was published today in Nature Chemical ...

FDA approves cresemba for serious fungal infections

March 9, 2015

(HealthDay)—Cresemba (isavuconazonium sulfate) has been approved by the U.S. Food and Drug Administration to treat invasive aspergillosis and invasive mucormycosis, the agency said Friday in a news release.

Fatal fungal infections resist newest class of drugs

September 7, 2011

Fungi that cause severe infections in those with compromised immune systems are resisting the action of the latest group of antifungal drugs. Uncovering their strategies for doing this will lead to more effective treatments, ...

Recommended for you

Space-inspired speed breeding for crop improvement

November 16, 2018

Technology first used by NASA to grow plants extra-terrestrially is fast tracking improvements in a range of crops. Scientists at John Innes Centre and the University of Queensland have improved the technique, known as speed ...

Cells decide when to divide based on their internal clocks

November 16, 2018

Cells replicate by dividing, but scientists still don't know exactly how they decide when to split. Deciding the right time and the right size to divide is critical for cells – if something goes wrong it can have a big ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.