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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Huvudupphovsmän: | , , , , , , , , , , , , , , , , , , , , , , |
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Materialtyp: | Artikel |
Språk: | engelska |
Publicerad: |
Philipps-Universität Marburg
2024
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Sammanfattning: | 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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Beskrivning: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
DOI: | 10.1038/s41467-023-41372-w |