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| Status |
Public on Mar 03, 2020 |
| Title |
Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Nicotinamide adenine dinucleotide (NAD), a cofactor for hundreds of metabolic reactions in all cell types, plays an essential role in diverse cellular processes including metabolism, DNA repair, and aging. NAD metabolism is critical to maintain cellular homeostasis in response to environmental signals, however, how it is impacted by the environment remains unclear. Here, we report an unexpected trans-kingdom cooperation between bacteria and mammalian cells wherein bacteria contribute to host NAD biosynthesis. Bacteria confer mammalian cells with the resistance to inhibitors of NAMPT, the rate limiting enzyme in the main vertebrate NAD salvage pathway. Mechanistically, a microbial nicotinamidase (PncA) that converts nicotinamide to nicotinic acid, a key precursor in the alternative deamidated NAD salvage pathway, is necessary and sufficient for this protective effect. This bacteria-enabled bypass of the pharmacologically induced metabolic block in mammalian cells represents a novel paradigm in drug resistance. This host-microbe metabolic interaction also dramatically enhances the hepatic NAD-boosting efficiency of nicotinamide and nicotinamide riboside supplementation, demonstrating a crucial role of microbes, gut microbiota in particular, in systemic NAD metabolism.
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| Overall design |
Comparison of the effects of an NAMPT inhibitor, STF118804, on the transcriptomes of clean and mycoplasma-infected tumors.
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| Contributor(s) |
Shats I, Xu X, Li JL, Li X |
| Citation(s) |
32130883 |
| Submission date |
Mar 02, 2019 |
| Last update date |
Mar 09, 2020 |
| Contact name |
Jian-Liang Li |
| Organization name |
NIEHS
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| Street address |
111 TW Alexander Dr
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| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA525242 |
| SRA |
SRP187342 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127750_RAW.tar |
7.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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