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Safe and Effective Antifungal Gleaned From Sea Squirt

Scientists announced Thursday they have discovered a nontoxic antifungal compound that destroys drug resistant strains of deadly fungi, a discovery that could save millions of lives.

(CN) — Scientists announced Thursday they have discovered a nontoxic antifungal compound that destroys drug resistant strains of deadly fungi, a discovery that could save millions of lives.

Researchers at the University of Wisconsin-Madison, combing the ocean for novel antimicrobials from understudied ecosystems, found the new molecule in the microbiome of a sea squirt. They named the antifungal turbinmicin after the Florida Keys sea creature Ecteinascidia turbinata, shaped like wide-necked bottles, from which it was isolated.

The findings, published in the journal Science, are the result of a collaboration between chemists, biologists and physicians working on a five-year $30 million grant from the National Institutes of Health to help develop new antimicrobial drugs.

Most antimicrobials are isolated from bacteria in soil, causing scientists who probe these bacteria for new drugs to find the same molecules repeatedly.

“Bacteria in particular are rich sources of molecules,” explained Tim Bugni, a professor in the UW-Madison School of Pharmacy who led the project, in a statement. “But a lot of the terrestrial ecosystems have been pretty heavily mined for drug discovery. There's immense bacterial diversity in the marine environment and it's barely been investigated at all.”

Bugni partnered with UW School of Medicine and Public Health infectious disease professor David Andes and UW-Madison bacteriology professor Cameron Currie to screen marine animals for new kinds of antimicrobial compounds.

Between 2012 and 2016, researchers traveled to the Florida Keys to collect saltwater invertebrates from which they grew nearly 1,500 strains of actinobacteria — the same kind of bacteria that has produced many clinical antibiotics. They tested 174 strains against drug-resistant Candida, a disease-causing fungus that is becoming increasingly deadly.

“Candida auris in particular is pretty nasty,” says Bugni. “The Candida auris strain we targeted in this paper is resistant to all three classes” of existing antifungals.”

Those initial tests revealed the effectiveness of turbinmicin, which in laboratory conditions slowed or destroyed nearly all fungal strains at low concentrations. Subsequent experiments in mice infected with drug-resistant strains of Candida auris and Aspergillus fumigatus demonstrated turbinmicin's ability to attack resistant fungi.

Yeast experiments by UW-Madison genetics professor Anjon Audhya demonstrated how turbinmicin targets the cellular packaging and organizational system of fungi.

Surprisingly, turbinmicin did not show toxic side effects in mice, even at concentrations 1000 times higher than the minimum dose.

Identifying compounds like turbinmicin is essential to developing new drugs to fight fungi, which kill increasing numbers of people by evolving resistance to drug treatments. But additional study and extensive preclinical research are necessary before turbinmicin becomes widely available.

Bugni and his colleagues have submitted a patent for turbinmicin while they improve the molecule by altering its structure to increase its effectiveness as a drug.

Discovering turbinmicin also validates efforts to explore new ecosystems for new antimicrobial candidates.

“Now we have the tools to sort through candidates, find promising strains and produce molecules to do animal studies,” says Bugni. “That’s the key for targeting multidrug resistance: you need unique molecules.”

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