Given the success of Volume I of this Research Topic, and how rapid the subject area is evolving, we are pleased to announce the launch of NAD+ Metabolism as a Novel Target Against Infection - Volume II.

Fundamental discoveries in the history of science, have identified nicotinamide adenine dinucleotide (NAD+) as an essential metabolite and the most important cross-kingdom electron carrier. Work from a plethora of Nobel Prize winners in the last century have highlighted the important role of NAD+ in cellular energy generation and redox biology. However, only in the last decade has the paramount importance of the non-redox functions of NAD+ been highlighted. In particular, NAD+ has been shown to participate in several physiological and pathological processes associated with DNA repair (PARPs), transcriptional regulation (sirtuins), secondary messenger signaling (CD38). Alteration in NAD+ synthesis is critical in incredibly diverse pathological conditions, ranging from neurodegeneration to cancer, diabetes to ischemia, and dysmetabolic diseases to inflammatory disorders. The recent advancements in understanding the biological functions of NAD+-consuming enzymes and the role of NAD+ biosynthetic routes have shown that targeting NAD+ has very promising potential for therapeutic treatment of various degenerative disorders. However, the processes that regulate the availability of NAD+ during infection at the molecular and cellular level are not currently understood.

Bacterial resistance to antibiotics could be the leading cause of death world-wide in the future. Therefore, it is of paramount importance to identify novel antimicrobial therapeutic tools. In this context the use of unconventional approaches to dissect NAD+ metabolism and its impact on different defense mechanisms could reveal new therapeutic targets. 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. The increasingly rapid spread of drug-resistant bacterial strains has encouraged scientists to intensify studies to identify new enzymes taking part in NAD+ metabolism. Unraveling the role, in pathogens and host cells, of newly discovered enzymes involved in NAD+ turnover during infection could increase our knowledge of the of bacterial pathogenesis and may be relevant for the development of targeted drug therapies against super bugs and reduce antibiotic resistance.

This Research Topic is focused on, but not limited to, studies aiming to evaluate the possibility of inducing anti-microbial host defense, modulating NAD+ metabolism. Advances in the study of this topic include:
• Discovery of new metabolites produced by NAD+ consuming enzymes and their role in signal transduction
• Identification of novel biosynthetic pathways in bacteria and plants and how they contribute to the responses to infections
• NAD+-synthesizing and NAD+-consuming enzymes as important molecular targets
• Minimizing potential side effects of NAD+-targeted treatment
• Work related to autophagy and mitophagy activation using NAD+-related metabolites, which could uncover novel tools to eliminate pathogens
• The NAD+ metabolome in pathogens and microbiota

Investigators can contribute with high-quality original research, short communications and reviews summarizing the most relevant information in the field.

Doctor Migaud is partially funded by Elysium Health. All other Topic Editors declare no competing interests.

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