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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Xue Kang & Alex Kirui & Artur Muszyński & Malitha C. Dickwella Widanage & Adrian Chen & Parastoo Azadi & Ping Wang & Frederic Mentink-Vigier & Tuo Wang, 2018. "Molecular architecture of fungal cell walls revealed by solid-state NMR," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05199-0
    DOI: 10.1038/s41467-018-05199-0
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    Cited by:

    1. Arnab Chakraborty & Liyanage D. Fernando & Wenxia Fang & Malitha C. Dickwella Widanage & Pingzhen Wei & Cheng Jin & Thierry Fontaine & Jean-Paul Latgé & Tuo Wang, 2021. "A molecular vision of fungal cell wall organization by functional genomics and solid-state NMR," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Malitha C. Dickwella Widanage & Isha Gautam & Daipayan Sarkar & Frederic Mentink-Vigier & Josh V. Vermaas & Shi-You Ding & Andrew S. Lipton & Thierry Fontaine & Jean-Paul Latgé & Ping Wang & Tuo Wang, 2024. "Adaptative survival of Aspergillus fumigatus to echinocandins arises from cell wall remodeling beyond β−1,3-glucan synthesis inhibition," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Qinghui Cheng & Malitha C. Dickwella Widanage & Jayasubba Reddy Yarava & Ankur Ankur & Jean-Paul Latgé & Ping Wang & Tuo Wang, 2024. "Molecular architecture of chitin and chitosan-dominated cell walls in zygomycetous fungal pathogens by solid-state NMR," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Liyanage D. Fernando & Yordanis Pérez-Llano & Malitha C. Dickwella Widanage & Anand Jacob & Liliana Martínez-Ávila & Andrew S. Lipton & Nina Gunde-Cimerman & Jean-Paul Latgé & Ramón Alberto Batista-Ga, 2023. "Structural adaptation of fungal cell wall in hypersaline environment," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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