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Natural Products

Fungus fighter from the sea

Molecule from the sea squirt microbiome battles deadly fungal infections in a new way

by Bethany Halford
November 19, 2020 | APPEARED IN VOLUME 98, ISSUE 45

 

Within the microbiome of the humble sea quirt, scientists have found a molecule that fights the deadly, drug-resistant fungus Candida auris. The compound, named turbinmicin, kills fungi via a mechanism of action that’s distinct from those of drugs in doctors’ current arsenal of antifungals.

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Doctors currently have access to only three classes of antifungal drugs, and those are becoming ineffective at fighting certain fungi, says David R. Andes, a physician at the University of Wisconsin–Madison who led the discovery effort with UW colleague Tim S. Bugni, an expert in marine natural products. C. auris infections, which can be deadly and spread rapidly, are commonly resistant to existing drugs. Once this fungus is in a hospital or nursing home, “it’s not uncommon for a large percentage of patients to get infections,” Andes says.

Andes and Bugni’s team screened compounds made by 1,482 bacteria from marine invertebrates harvested in the Florida Keys. Their approach used metabolomics and genomics to find bacteria that made unusual metabolites.

The researchers homed in on one unusual metabolite made by bacteria in the gut of the sea squirt that dwells in shallow waters. The compound, dubbed turbinmicin, kills C. auris and other drug-resistant fungi in test tubes and in mice. What’s more, there were no toxic side effects, even when mice were given doses of turbinmicin 100 times the amount necessary to stop the infection. Mechanistic studies show that turbinmicin kills fungi in a novel way, by disrupting a protein needed to transport phospholipids between cells and organelles (Science 2020, DOI: 10.1126/science.abd6919).

“We know that the unusual life histories of sea squirts, sponges, slugs, and seaweeds have selected for specialized relationships with microbes based on shared chemistry,” Julia Kubanek, an expert on developing drugs from marine organisms at the Georgia Institute of Technology, says in an email. “It’s great to see that diverse chemistry explored systematically with metabolomic techniques, leading to the discovery of new potential drugs.”

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