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Paired with SOLBacteria defend against phage infection through a variety of antiphage defence systems-.Many defence systems were recently shown to deplete cellular nicotinamide adeninedinucleotide (NAD*) in response to infection, by cleaving NAD* into ADP-ribose (ADPR) andnicotinamide234562, it was demonstrated that NAD* depletion during infection deprives thephage ofthis essential molecule and impedes phage replication. Here we show that asubstantial fraction of phages possess enzymatic pathways allowing reconstitution ofNADfrom its degradation products in infected cells. We describe NAD* reconstitution pathway1(NARP1), a two-step pathway in which one enzyme phosphorylates ADPR to generate ADPRpyrophosphate (ADPR-PP), and the second enzyme conjugates ADPR-PP and nicotinamide togenerate NAD*. Phages encoding NARPl can overcome a diverse set ofdefence systems.including Thoeris, DSRl, DSR2, SIR2-HerA and SEFIR, all of which deplete NAD* as part oftheir defensive mechanism. Phylogenetic analyses show that NARPl is primarily encoded onphage genomes, suggesting a phage-specifc function in countering bacterial defences. Apathway, NARP2, allows phages to overcome bacterial defences by building NAD*
