Breaking down the wall: Solid-state NMR illuminates how fungi build and remodel diverse cell walls

Summary

Scientists have developed a new technique called solid-state NMR that can examine fungal cell walls without damaging them, revealing how these structures are built and reorganized. This research shows that different fungi have different wall architectures made of sugar-like molecules including chitin and various glucans, and that fungi can quickly adapt their walls when exposed to antifungal drugs. These findings could help develop better antifungal treatments by targeting the specific structural features that different fungi rely on for survival.

Background

Fungal cell walls are essential organelles composed of complex polymers including chitin, glucans, and mannans that vary significantly across species. Traditional biochemical methods using harsh treatments like alkali extraction alter the native organization of cell wall polymers, making it difficult to understand true in vivo structure.

Objective

This review explains how solid-state nuclear magnetic resonance (ssNMR) spectroscopy has advanced understanding of fungal cell wall architecture and remodeling mechanisms without physically disrupting native structures. The authors demonstrate how ssNMR reveals molecular-level details of cell wall organization across diverse fungal species and under various stress conditions.

Results

ssNMR studies revealed distinct cell wall architectures across multiple fungal species, including polymorphic forms of chitin, chitosan, and glucans with specific functional roles. Under caspofungin treatment, A. fumigatus undergoes seven major structural remodeling mechanisms including enhanced chitin biosynthesis, altered glucan interactions, and surface charge reduction. Similar adaptive responses occur in C. albicans and C. auris under echinocandin exposure.

Conclusion

ssNMR provides unprecedented atomic-level resolution of fungal cell wall organization and dynamics, revealing both universal design principles and species-specific adaptations. This approach complements classical methods and offers transformative potential for understanding fungal pathophysiology, virulence mechanisms, and developing novel antifungal strategies.
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