Phages reconstitute NAD+ to counter bacterial immunity.

Autor: Osterman, Ilya, Samra, Hadar, Rousset, Francois, Loseva, Elena, Itkin, Maxim, Malitsky, Sergey, Yirmiya, Erez, Millman, Adi, Sorek, Rotem
Zdroj: Nature; Oct2024, 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.A study shows that many phages are capable of evading antiphage defence systems of bacteria by reconstituting NAD+ from its degradation products in infected cells. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz: