A groundbreaking study from Michigan State University (MSU), recently published in Nature Communications, has revealed how the multidrug-resistant superfungus Candida auris uniquely reconstructs its cell wall to survive antifungal treatments. The discovery marks a significant step toward understanding and combating one of the most dangerous fungal pathogens threatening hospitalized patients worldwide.
Led by Tuo Wang, a Carl Brubaker Endowed Professor at Department of Chemistry, the research compares C. auris with its more common relative, Candida albicans. While both species share similar cell wall structures, the study shows they deploy markedly different strategies to resist echinocandins — a class of frontline antifungal drugs.
"Invasive infections by Candida species are a growing threat, especially with the rise of drug-resistant species like C. auris and complications from COVID-19-related candidiasis," said Wang. "Our study provides high-resolution insight into how these fungi adapt to treatment."
Using advanced solid-state nuclear magnetic resonance spectroscopy, the team found that both fungi experience stiffening of key cell wall polysaccharides—such as β-1,6-glucans and mannan sidechains—when treated with the antifungal drug caspofungin. However, while C. albicans thickens its cell wall and alters chitin and glucan dynamics in response, C. auris takes a different approach: it increases production of β-1,6-glucan to preserve its structural integrity.
The study also sheds light on the long-mysterious role of β-1,6-glucan, an underexplored component of fungal cell walls that appears to play a critical role in drug resistance. "Gene deletion and subsequent structural analysis revealed that β-1,6-glucan is directly tied to how C. auris responds to antifungal drugs like micafungin and caspofungin," Wang explained.
The interdisciplinary research team included MSU graduate students Kalpana Singh and Malitha Dickwella Widanage, visiting scholar Yifan Xu (now entering MSU's Chemistry PhD program), and postdoctoral associate Jayasubba Reddy Yarava.
This interdisciplinary effort was strengthened by contributions from leading microbiologists, including Dr. Frederic Lamoth's team at Lausanne University Hospital and the University of Lausanne (Switzerland), Dr. Neil A. R. Gow of the University of Exeter (UK), and Dr. Ping Wang of Louisiana State University Health Sciences Center. The research also benefited from access to state-of-the-art instrumentation at the National High Magnetic Field Laboratory (Tallahassee, Florida), with technical support from Dr. Frederic Mentink-Vigier and Dr. Faith Scott.
Ultimately, the research not only clarifies how C. auris survives drug treatment but also offers a roadmap for designing more effective antifungal therapies in the future by targeting species-specific structural adaptations.
