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Molecular architecture of fungal cell walls revealed by solid-state NMR

Xue Kang, Alex Kirui, Artur Muszyński, Malitha C. Dickwella Widanage, Adrian Chen, Parastoo Azadi, Ping Wang, Frederic Mentink-Vigier and Tuo Wang ()
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Xue Kang: Louisiana State University
Alex Kirui: Louisiana State University
Artur Muszyński: University of Georgia
Malitha C. Dickwella Widanage: Louisiana State University
Adrian Chen: Louisiana State University
Parastoo Azadi: University of Georgia
Ping Wang: Louisiana State University Health Sciences Center
Frederic Mentink-Vigier: National High Magnetic Field Laboratory
Tuo Wang: Louisiana State University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract The high mortality of invasive fungal infections, and the limited number and inefficacy of antifungals necessitate the development of new agents with novel mechanisms and targets. The fungal cell wall is a promising target as it contains polysaccharides absent in humans, however, its molecular structure remains elusive. Here we report the architecture of the cell walls in the pathogenic fungus Aspergillus fumigatus. Solid-state NMR spectroscopy, assisted by dynamic nuclear polarization and glycosyl linkage analysis, reveals that chitin and α-1,3-glucan build a hydrophobic scaffold that is surrounded by a hydrated matrix of diversely linked β-glucans and capped by a dynamic layer of glycoproteins and α-1,3-glucan. The two-domain distribution of α-1,3-glucans signifies the dual functions of this molecule: contributing to cell wall rigidity and fungal virulence. This study provides a high-resolution model of fungal cell walls and serves as the basis for assessing drug response to promote the development of wall-targeted antifungals.

Date: 2018
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DOI: 10.1038/s41467-018-05199-0

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