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

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.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1];  [1];  [2]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [1]
  1. Louisiana State Univ., Baton Rouge, LA (United States)
  2. Univ. of Georgia, Athens, GA (United States)
  3. Louisiana State Univ. Health Sciences Center, New Orleans, LA (United States)
  4. Florida State Univ., Tallahassee, FL (United States). National High Magnetic Field Lab. (MagLab)
Publication Date:
Research Org.:
Univ. of Georgia, Athens, GA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Chemical Sciences, Geosciences & Biosciences Division
OSTI Identifier:
1511439
Grant/Contract Number:  
SC0015662
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Kang, Xue, Kirui, Alex, Muszyński, Artur, Widanage, Malitha C. Dickwella, Chen, Adrian, Azadi, Parastoo, Wang, Ping, Mentink-Vigier, Frederic, and Wang, Tuo. Molecular architecture of fungal cell walls revealed by solid-state NMR. United States: N. p., 2018. Web. doi:10.1038/s41467-018-05199-0.
Kang, Xue, Kirui, Alex, Muszyński, Artur, Widanage, Malitha C. Dickwella, Chen, Adrian, Azadi, Parastoo, Wang, Ping, Mentink-Vigier, Frederic, & Wang, Tuo. Molecular architecture of fungal cell walls revealed by solid-state NMR. United States. doi:10.1038/s41467-018-05199-0.
Kang, Xue, Kirui, Alex, Muszyński, Artur, Widanage, Malitha C. Dickwella, Chen, Adrian, Azadi, Parastoo, Wang, Ping, Mentink-Vigier, Frederic, and Wang, Tuo. Mon . "Molecular architecture of fungal cell walls revealed by solid-state NMR". United States. doi:10.1038/s41467-018-05199-0. https://www.osti.gov/servlets/purl/1511439.
@article{osti_1511439,
title = {Molecular architecture of fungal cell walls revealed by solid-state NMR},
author = {Kang, Xue and Kirui, Alex and Muszyński, Artur and Widanage, Malitha C. Dickwella and Chen, Adrian and Azadi, Parastoo and Wang, Ping and Mentink-Vigier, Frederic and Wang, Tuo},
abstractNote = {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.},
doi = {10.1038/s41467-018-05199-0},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {7}
}

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Works referenced in this record:

A simple and rapid method for the permethylation of carbohydrates
journal, August 1984