| Autor: |
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 |
| Předmět: |
|
| Zdroj: |
Nature Communications; 10/2/2023, Vol. 14 Issue 1, p1-16, 16p |
| Abstrakt: |
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+. Streptococcus pneumoniae is a common cause of lower respiratory tract infection. Here, Klabunde et al. present a transcriptomic, metabolomic and proteomic characterisation of the bronchial epithelial cell response to infection and show that NAD+ has a role in controlling bacterial replication. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Full text from SpringerLink