Journal Article

A molecular vision of fungal cell wall organization by functional genomics and solid-state NMR

Chakraborty, Arnab, Wei, Pingzhen, Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF) ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Jin, Cheng, Dickwella Widanage, Malitha, This work was supported by the National Institutes of Health (NIH) grant AI149289 toT.W. Preparation of isotopically labeled samples was supported by the Bagui ScholarProgram Fund of Guangxi Zhuang Autonomous Region 2016A24 to C.J. A portion ofthis work was performed at the National High Magnetic Field Laboratory, which issupported by the National Science Foundation Cooperative Agreement No. DMR-1644779 and the State of Florida, Wang, Tuo, Fontaine, Thierry, Latgé, Jean-Paul, Guangxi Academy of Sciences [Nanning, China], Louisiana State University [BatonRouge] (LSU), Fang, Wenxia, University of Crete [Heraklion] (UOC), Fernando, Liyanage

2021

Overview

Abstract Vast efforts have been devoted to the development of antifungal drugs targeting the cell wall, but the supramolecular architecture of this carbohydrate-rich composite remains insufficiently understood. Here we compare the cell wall structure of a fungal pathogen Aspergillus fumigatus and four mutants depleted of major structural polysaccharides. High-resolution solid-state NMR spectroscopy of intact cells reveals a rigid core formed by chitin, β-1,3-glucan, and α-1,3-glucan, with galactosaminogalactan and galactomannan present in the mobile phase. Gene deletion reshuffles the composition and spatial organization of polysaccharides, with significant changes in their dynamics and water accessibility. The distribution of α-1,3-glucan in chemically isolated and dynamically distinct domains supports its functional diversity. Identification of valines in the alkali-insoluble carbohydrate core suggests a putative function in stabilizing macromolecular complexes. We propose a revised model of cell wall architecture which will improve our understanding of the structural response of fungal pathogens to stresses.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 101/6 / 140/131 / 631/326/193 / 631/326/193/2538 / 631/45/72/1205 / 631/535/878/1264 / 639/638/11/878/1264 / Alkalies / Alkalies - pharmacology / Antifungal Agents / Aspergillus fumigatus / Aspergillus fumigatus - drug effects / Aspergillus fumigatus - genetics / Aspergillus fumigatus - metabolism / beta-Glucans / beta-Glucans - chemistry / Biochemistry, Molecular Biology / Carbohydrates / Cell Wall / Cell Wall - chemistry / Cell Wall - metabolism / Cell walls / Chitin / Chitin - chemistry / Drug delivery / Drug development / Functional morphology / Fungal Proteins / Fungal Proteins - genetics / Fungi / Fungi - drug effects / Fungi - genetics / Fungi - metabolism / Fungicides / Galactose / Galactose - analogs & derivatives / Gene Deletion / Genomics / Glucan / Glucans / Glucans - chemistry / Glycoproteins / Humanities and Social Sciences / Life Sciences / Macromolecules / Magnetic Resonance Spectroscopy / Magnetic Resonance Spectroscopy - methods / Mannans / multidisciplinary / Mutants / Mutation / NMR / NMR spectroscopy / Nuclear magnetic resonance / Pathogens / Polysaccharides / Saccharides / Science / Science (multidisciplinary) / Solid state / Spectroscopy / Spectrum analysis / Structural Biology / Structural response / β-1,3-Glucan
• ISBN: 9780007144518, 0007144512