DOI: 10.1101/489674Dec 7, 2018Paper

Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway

BioRxiv : the Preprint Server for Biology
Igor ShatsXiaoling Li

Abstract

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 the environment, and disruption of this homeostasis is associated with decreased cellular NAD levels in aging. Conversely, elevated NAD synthesis is required to sustain the increased metabolic rate of cancer cells. Consequently, therapeutic strategies aimed to both upregulate NAD (i.e. NAD-boosting nutriceuticals) or downregulate NAD (inhibitors of key NAD synthesis enzymes) are being actively investigated. However, how this essential metabolic pathway 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 cancer 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 neces...Continue Reading

Related Concepts

Aging
Drug Resistance
Environment
Metabolism
Nicotinamide adenine dinucleotide (NAD)
Niacin
Nicotinamidase
Vertebrates
Chemical cofactor
Dysplastic Nevus

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