Editorial: NAD+ metabolism as a novel target against infection–Volume II

Fundamental discoveries in the history of science, including research from four Nobel laureates, have identified the pyrimidine nucleotide, nicotinamide adenine dinucleotide (NAD+) as an essential metabolite and the most important cross-kingdom electron carrier. While a wealth of scientific studies in the last century have highlighted the important role of NAD+ in cellular energy generation and redox biology, recent studies have provided evidence for the paramount importance of the non-redox functions of NAD+. Alteration in intracellular NAD+ concentrations is critical in several pathological conditions, including but not limited to neurodegenerative diseases, cancer, diabetes, ischemia injury, dysmetabolic diseases, and inflammatory disorders. Recent advances in our understanding of the biological functions of NAD+-consuming enzymes and the role of NAD+ biosynthetic routes have shown that targeting NAD+ metabolism has very promising potential for therapeutic treatment of infectious diseases. Bacterial resistance to antibiotics is considered one of the greatest threats to human health. Cases of antibiotic resistance are constantly emerging, and the time needed for bacteria to become resistant to newly introduced antibiotics, is getting shorter. Therefore, it is crucial to identify antimicrobials with new mechanism of action to use as therapeutic tools. In this context, modulation of host NAD+ metabolism by the activation or inhibition of key enzymes could influence NAD+ signaling pathways in pathogens and their ability to colonize host cells. Further, the discovery of the enzymes involved in NAD+ turnover in the host during infection could increase our knowledge of bacterial pathogenesis and may be relevant for the development of targeted drug therapies against antibiotic resistant bacteria. However, detailed mechanisms by which NAD+ acts as a regulator and how we can target NAD+ metabolism during microbial infections is still poorly understood.