A strain of Candida auris cultured in a petri dish at a CDC laboratory. Credit: Shawn Lockhart/CDC
In 2016, the first clinical case of Candida auris was reported in the United States. Fifty more cases were reported that year—a trend that would continue at a startling rate. In 2023, 4,514 cases of C. auris were reported, an increase of more than 1,500 cases over the previous year, and nearly 3,000 compared with 2021.
Not considered a problem only 15 years ago, C. auris now sits atop the World Health Organization’s list of priority fungal pathogens. However, unlike the dozens of classes of antibiotics available for infections, there are only three classes of antifungals on the market right now.
Researchers at McMaster University are trying to change that. In the university’s greenhouse, a research team isolated new molecules—dubbed coniotins—from a plant-dwelling fungus called Coniochaeta hoffmannii. The team says their discovery responds to a critical need for new antifungal medicines.
From feet to blood
C. auris is particularly problematic for individuals with compromised immune systems, like cancer patients undergoing chemotherapy. It is spread easily among sick patients in healthcare facilities. The fungus can cause a range of infections from skin infections like athlete’s foot to more severe, life-threatening infections that target the lungs, the bloodstream, and the nervous system.
Although disease-causing fungi are microscopic like bacteria and viruses, they’re more closely related to humans than they are to other microbes—meaning treatments that kill fungi tend to kill human cells too. However, that is not the case with McMaster’s new molecules.
In a paper published in Nature Communications, the research team demonstrated that coniotins not only attack C. auris and several other fungal pathogens, but do so without harming human cells.
In fact, they function unlike any other antifungal on the market. Where most target proteins and membranes, coniotins instead bind to the fungal cell wall— a protective shell that provides structural integrity for what’s inside. Disturbing this structure, as coniotins do, fundamentally changes how well the organism can survive.
Xufei Chen, a postdoctoral fellow and first-author on the new paper, identified the new drug class through a process called prefractionation, which allows scientists to tease specific molecules out from complex chemical mixtures.
“Since the golden age of antibiotic discovery, progress has slowed, due primarily to the frequent rediscovery of known compounds,” she says. “To address this, we implemented a prefractionation screening approach to target overlooked or masked metabolites. By integrating mass spectrometry, metabolomics, and computational analysis, I was able to discover this previously hidden molecule.”
Using this same process, the team recently discovered a new class of antibiotics. They have also used prefractionation to identify several other new drug candidates, which remain under study.
“What’s really amazing is that we’ve only screened about 5 percent of the chemical library we’ve built here at McMaster,” said Gerry Wright, professor of biochemistry at McMaster and PI on the new study. “We have an immense, largely unexplored chemical space at our fingertips, and a cost-effective way to reduce the rediscovery of known compounds. Who knows what else is in there?”
Wright and his team are moving coniotins along the development pathway. The next steps include producing it at scale through fermentation, and formulating the new drug class so it may eventually be suitable for IV delivery.