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Series GSE127750 Query DataSets for GSE127750
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
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.
Overall design Comparison of the effects of an NAMPT inhibitor, STF118804, on the transcriptomes of clean and mycoplasma-infected tumors.
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
Street address 111 TW Alexander Dr
City Durham
State/province NC
ZIP/Postal code 27709
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (16)
GSM3638062 clean_con_1
GSM3638063 clean_con_3
GSM3638064 clean_con_4
BioProject PRJNA525242
SRA SRP187342

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Supplementary file Size Download File type/resource
GSE127750_RAW.tar 7.7 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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