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

Klabunde, Björn; Wesener, André; Bertrams, Wilhelm; Beinborn, Isabell; Paczia, Nicole; Surmann, Kristin; Blankenburg, Sascha; Wilhelm, Jochen; Serrania, Javier; Knoops, Kèvin; Elsayed, Eslam M.; Laakmann, Katrin; Jung, Anna Lena; Kirschbaum, Andreas; Hammerschmidt, Sven; Alshaar, Belal; Gisch, Nicolas; Abu Mraheil, Mobarak; Becker, Anke; Völker, Uwe; Vollmeister, Evelyn; Benedikter, Birke J.; Schmeck, Bernd

doi:10.1038/s41467-023-41372-w

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

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Paczia, Nicole
Core Facility Metabolomics and small Molecules Mass Spectrometry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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https://doi.org/10.1038/s41467-023-41372-w
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Citation

Klabunde, B., Wesener, A., Bertrams, W., Beinborn, I., Paczia, N., Surmann, K., et al. (2023). NAD⁺ metabolism is a key modulator of bacterial respiratory epithelial infections. Nature Communications, 14(1): 5818. doi:10.1038/s41467-023-41372-w.

Cite as: https://hdl.handle.net/21.11116/0000-000D-C4AE-2

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+.