| Autor: |
Osterman, Ilya, Samra, Hadar, Rousset, Francois, Loseva, Elena, Itkin, Maxim, Malitsky, Sergey, Yirmiya, Erez, Millman, Adi, Sorek, Rotem |
| Zdroj: |
Nature; October 2024, Vol. 634 Issue: 8036 p1160-1167, 8p |
| Abstrakt: |
Bacteria defend against phage infection through a variety of antiphage defence systems1. Many defence systems were recently shown to deplete cellular nicotinamide adenine dinucleotide (NAD+) in response to infection, by cleaving NAD+into ADP-ribose (ADPR) and nicotinamide2–7. It was demonstrated that NAD+depletion during infection deprives the phage of this essential molecule and impedes phage replication. Here we show that a substantial fraction of phages possess enzymatic pathways allowing reconstitution of NAD+from its degradation products in infected cells. We describe NAD+reconstitution pathway 1 (NARP1), a two-step pathway in which one enzyme phosphorylates ADPR to generate ADPR pyrophosphate (ADPR-PP), and the second enzyme conjugates ADPR-PP and nicotinamide to generate NAD+. Phages encoding NARP1 can overcome a diverse set of defence systems, including Thoeris, DSR1, DSR2, SIR2–HerA and SEFIR, all of which deplete NAD+as part of their defensive mechanism. Phylogenetic analyses show that NARP1 is primarily encoded on phage genomes, suggesting a phage-specific function in countering bacterial defences. A second pathway, NARP2, allows phages to overcome bacterial defences by building NAD+using metabolites different from ADPR-PP. Our findings reveal a unique immune evasion strategy in which viruses rebuild molecules depleted by defence systems, thus overcoming host immunity. |
| Databáze: |
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