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

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

Nature communications (2023-10-03)
Björn Klabunde, André Wesener, Wilhelm Bertrams, Isabell Beinborn, Nicole Paczia, Kristin Surmann, Sascha Blankenburg, Jochen Wilhelm, Javier Serrania, Kèvin Knoops, Eslam M Elsayed, Katrin Laakmann, Anna Lena Jung, Andreas Kirschbaum, Sven Hammerschmidt, Belal Alshaar, Nicolas Gisch, Mobarak Abu Mraheil, Anke Becker, Uwe Völker, Evelyn Vollmeister, Birke J Benedikter, Bernd Schmeck
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+.

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BEAS-2B Cell Line human
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