Titel: | NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections |
Autor: | Klabunde, Björn |
Weitere Verfasser: | 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; Völker, Uwe; Vollmeister, Evelyn; Benedikter, Birke J.; Schmeck, Bernd; ; |
Veröffentlicht: | 2024 |
URI: | https://archiv.ub.uni-marburg.de/es/2024/0875 |
URN: | urn:nbn:de:hebis:04-es2024-08758 |
DOI: | https://doi.org/10.1038/s41467-023-41372-w |
DDC: | 610 Medizin |
Publikationsdatum: | 2024-04-18 |
Lizenz: | https://creativecommons.org/licenses/by/4.0 |
Schlagwörter: |
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Pathogens, Molecular medicine, Bacterial infection, Antimicrobial responses |
Summary:
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+.
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