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

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

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 dysregulat...

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Main Authors: 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, Völker, Uwe, Vollmeister, Evelyn, Benedikter, Birke J., Schmeck, Bernd,
Format: Article
Language:English
Published: Philipps-Universität Marburg 2024
Subjects:
Pathogens
Medizin
Molecular medicine
Bacterial infection
Antimicrobial responses
Medical sciences Medicine
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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+.
Item Description:Gefördert durch den Open-Access-Publikationsfonds der UB Marburg.
DOI:10.1038/s41467-023-41372-w

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