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Potent, puzzling and (now less) toxic: Team discovers how antifungal drug works
Date:4/15/2014

CHAMPAIGN, Ill. Scientists have solved a decades-old medical mystery and in the process have found a potentially less toxic way to fight invasive fungal infections, which kill about 1.5 million people a year. The researchers say they now understand the mechanism of action of amphotericin, an antifungal drug that has been in use for more than 50 years even though it is nearly as toxic to human cells as it is to the microbes it attacks.

A report of the new findings appears in Nature Chemical Biology.

"Invasive fungal infections are a very important unmet medical need," said University of Illinois and Howard Hughes Medical Institute chemistry professor Martin Burke, who led the study with chemistry professor Chad Rienstra. "There are about 3 million cases per year and what's striking is that, even in 2014, half the patients who come into the hospital with an invasive fungal infection in their blood die."

More people are killed by invasive fungal infections than by malaria or tuberculosis, Burke said.

Amphotericin (am-foe-TEHR-ih-sin) is the most effective broad-spectrum antifungal drug available, Burke said. But its use is limited by its toxicity to human cells.

"When I was a medical student, they used to call it 'amphoterrible' in the clinic because it has very powerful side effects," he said. "And so you're stuck between having the fungus kill the patient, versus using too much amphotericin, which kills the patient."

Scientists have long sought to make amphotericin less toxic, but have been hindered by an obvious problem: Because it is so hard to study, no one knew exactly how it worked.

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Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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