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- W4366091750 abstract "Lower respiratory tract infections caused by Streptococcus pneumoniae (Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial 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 cascade in Spn infections, predicting a novel antibacterial mechanism of NAD+." @default.
- W4366091750 created "2023-04-19" @default.
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- W4366091750 date "2023-04-14" @default.
- W4366091750 modified "2023-10-03" @default.
- W4366091750 title "NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections" @default.
- W4366091750 doi "https://doi.org/10.1101/2023.04.13.536709" @default.
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