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NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections

Author

Listed:
  • Björn Klabunde

    (Philipps-Universität Marburg)

  • André Wesener

    (Philipps-Universität Marburg)

  • Wilhelm Bertrams

    (Philipps-Universität Marburg)

  • Isabell Beinborn

    (Philipps-Universität Marburg)

  • Nicole Paczia

    (Max Planck Institute for Terrestrial Microbiology)

  • Kristin Surmann

    (University Medicine Greifswald)

  • Sascha Blankenburg

    (University Medicine Greifswald)

  • Jochen Wilhelm

    (Institute for Lung Health (ILH)
    German Center for Lung Research (DZL))

  • Javier Serrania

    (Philipps-Universität Marburg)

  • Kèvin Knoops

    (Maastricht University)

  • Eslam M. Elsayed

    (Philipps-Universität Marburg
    Philipps-Universität Marburg
    Zagazig University)

  • Katrin Laakmann

    (Philipps-Universität Marburg)

  • Anna Lena Jung

    (Philipps-Universität Marburg
    Philipps-Universität Marburg)

  • Andreas Kirschbaum

    (University Hospital Gießen and Marburg (UKGM))

  • Sven Hammerschmidt

    (University of Greifswald)

  • Belal Alshaar

    (Leibniz Lung Center)

  • Nicolas Gisch

    (Leibniz Lung Center)

  • Mobarak Abu Mraheil

    (Justus-Liebig Universität Giessen)

  • Anke Becker

    (Philipps-Universität Marburg)

  • Uwe Völker

    (University Medicine Greifswald)

  • Evelyn Vollmeister

    (Philipps-Universität Marburg)

  • Birke J. Benedikter

    (Philipps-Universität Marburg
    Maastricht University)

  • Bernd Schmeck

    (Philipps-Universität Marburg
    Institute for Lung Health (ILH)
    Philipps-Universität Marburg
    Philipps-Universität Marburg)

Abstract

Lower respiratory tract infections caused by Streptococcus pneumoniae (Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial cellular response to Spn infection on a transcriptomic, proteomic and metabolic level. We found the NAD+ salvage pathway to be dysregulated upon infection in a cell line model, primary human lung tissue and in vivo in rodents, leading to a reduced production of NAD+. Knockdown of NAD+ salvage enzymes (NAMPT, NMNAT1) increased bacterial replication. NAD+ treatment of Spn inhibited its growth while growth of other respiratory pathogens improved. Boosting NAD+ production increased NAD+ levels in immortalized and primary cells and decreased bacterial replication upon infection. NAD+ treatment of Spn dysregulated the bacterial metabolism and reduced intrabacterial ATP. Enhancing the bacterial ATP metabolism abolished the antibacterial effect of NAD+. Thus, we identified the NAD+ salvage pathway as an antibacterial pathway in Spn infections, predicting an antibacterial mechanism of NAD+.

Suggested Citation

  • Björn Klabunde & André Wesener & Wilhelm Bertrams & Isabell Beinborn & Nicole Paczia & Kristin Surmann & Sascha Blankenburg & Jochen Wilhelm & Javier Serrania & Kèvin Knoops & Eslam M. Elsayed & Katri, 2023. "NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41372-w
    DOI: 10.1038/s41467-023-41372-w
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    References listed on IDEAS

    as
    1. Ilka Haferkamp & Stephan Schmitz-Esser & Nicole Linka & Claude Urbany & Astrid Collingro & Michael Wagner & Matthias Horn & H. Ekkehard Neuhaus, 2004. "A candidate NAD+ transporter in an intracellular bacterial symbiont related to Chlamydiae," Nature, Nature, vol. 432(7017), pages 622-625, December.
    2. Shin-ichiro Imai & Christopher M. Armstrong & Matt Kaeberlein & Leonard Guarente, 2000. "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase," Nature, Nature, vol. 403(6771), pages 795-800, February.
    3. Stephen J. Gardell & Meghan Hopf & Asima Khan & Mauro Dispagna & E. Hampton Sessions & Rebecca Falter & Nidhi Kapoor & Jeanne Brooks & Jeffrey Culver & Chris Petucci & Chen-Ting Ma & Steven E. Cohen &, 2019. "Boosting NAD+ with a small molecule that activates NAMPT," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

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