Mushroom fighter by the sea

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

Doctors currently have access to only three classes of antifungal drugs, and these are becoming ineffective at fighting certain fungi, says David R. Andes, a University of Wisconsin-Madison physician 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 examined compounds made from 1,482 marine invertebrate bacteria collected in the Florida Keys. Their approach used metabolomics and genomics to find bacteria that produced unusual metabolites.

The researchers focused on an unusual metabolite produced by bacteria in the gut of the marine sketch that resides in shallow water. The compound, nicknamed turbinmicin, kills C. auris and other drug resistant fungi in test tubes and mice. In addition, no toxic side effects occurred, even when the mice were given doses of turbinmicin 100 times the amount needed to stop the infection. Mechanistic studies show that turbinmicin kills fungi in a new 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 stories of sea splashes, sponges, snails and algae have been selected for specialized relationships with microbes based on shared chemistry,” says Julia Kubanek, an expert in drug development from marine organisms at the Georgia Institute of Technology. in an email. “It is fantastic to see diverse chemistry systematically explored with metabolomic techniques, leading to the discovery of new potential drugs.”