IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41372-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41372-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41372-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Liang Yang & Junfeng Shen & Chunhua Liu & Zhonghua Kuang & Yong Tang & Zhengjiang Qian & Min Guan & Yongfeng Yang & Yang Zhan & Nan Li & Xiang Li, 2023. "Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Shuai Zhang & Zhe Sun & Yuewen Qi & Xiaolu Fang & Hong Yu, 2018. "Prognostic and Clinicopathological Value of SIRT1 Expression in Female Reproductive System Cancer," International Journal of Sciences, Office ijSciences, vol. 7(01), pages 57-65, January.
    3. Xiangkai Zhen & Xiaolong Xu & Le Ye & Song Xie & Zhijie Huang & Sheng Yang & Yanhui Wang & Jinyu Li & Feng Long & Songying Ouyang, 2024. "Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Nicholas Sim & Jean-Michel Carter & Kamalakshi Deka & Benita Kiat Tee Tan & Yirong Sim & Suet-Mien Tan & Yinghui Li, 2024. "TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Beata Jablonska & Katrina L. Adams & Panagiotis Kratimenos & Zhen Li & Emma Strickland & Tarik F. Haydar & Katharina Kusch & Klaus-Armin Nave & Vittorio Gallo, 2022. "Sirt2 promotes white matter oligodendrogenesis during development and in models of neonatal hypoxia," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41372-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.