Wang Group Uncovers Secrets of the Fungal Cell Wall

 

Tuo Wang Assistant Professor Tuo Wang

The limited current repertoire of antifungal agents, their poor efficacy, and the high mortality rate of invasive fungal infections, necessitates the development of new drugs. The fungal cell wall is a promising target as it contains polysaccharides that are absent in humans. Unfortunately, our inadequate understanding of the cell wall structure has impeded this endeavor.

 

Pathogenic Funi, Solid State NMR, and Molecular Architecture

To address this issue, Dr Tuo Wang’s Laboratory has been developing dynamic nuclear polarization (DNP) solid-state NMR methods to elucidate the structure of intact and native fungal cell walls, in collaboration with Dr Ping Wang of the Department of Microbiology, Immunology and Parasitology at the LSU Health Sciences Center in New Orleans. Wang and Wang recently received funding from the Louisiana Biomedical Collaborative Research Program (LBCRP), for their project titled, “Solid-State NMR Studies of the Dynamic Structure of Aspergillus fumigatus Cell Walls.”

 

Wang Group

Group members beside the NMR magnet: Dr Xue Kang, Malitha Dickwella Widanage and Alex Kirui 

The research is primarily finished by the LSU Baton Rouge team, which includes the team leader, Dr Tuo Wang, a postdoctoral researcher, Dr Xue Kang, two graduate students, Alex Kirui and Malitha Dickwella Widanage, plus an undergraduate, Adrian Chen. Group members have traveled to collect data at the National High Magnetic Field Laboratory in Tallahassee, FL. Analyses of sugar composition has been conducted at the Complex Carbohydrate Research Center in Athens, GA.

Wang’s findings have recently been accepted for publication in Nature Communications.*  The study revealed the high-resolution architecture of the cell wall in a pathogenic fungus and has substantially revised our existing knowledge of Aspergillus fumigatus. The methods lay the foundation for further evaluating the binding site and the impact of antifungal agents, in intact cells, with molecular resolution. The results provide the structural and methodology basis for drug development.

*Xue Kang, Alex Kirui, Artur Muszyński, Malitha C Dickwella Widanage, Adrian Chen, Parastoo Azadi, Ping Wang, Frederic Mentink-Vigier, Tuo Wang “Molecular Architecture of Fungal Cell Walls Revealed by Solid-State NMR,” Nat. Commun. 9, 2747 (2018).