A conserved family of immune effectors cleaves cellular ATP upon viral infection

Francois Rousset, Erez Yirmiya, Shahar Nesher, Alexander Brandis, Tevie Mehlman, Maxim Itkin, Sergey Malitsky, Adi Millman, Sarah Melamed, Rotem Sorek

Research output: Contribution to journalArticlepeer-review


During viral infection, cells can deploy immune strategies that deprive viruses of molecules essential for their replication. Here, we report a family of immune effectors in bacteria that, upon phage infection, degrade cellular adenosine triphosphate (ATP) and deoxyadenosine triphosphate (dATP) by cleaving the N-glycosidic bond between the adenine and sugar moieties. These ATP nucleosidase effectors are widely distributed within multiple bacterial defense systems, including cyclic oligonucleotide-based antiviral signaling systems (CBASS), prokaryotic argonautes, and nucleotide-binding leucine-rich repeat (NLR)-like proteins, and we show that ATP and dATP degradation during infection halts phage propagation. By analyzing homologs of the immune ATP nucleosidase domain, we discover and characterize Detocs, a family of bacterial defense systems with a two-component phosphotransfer-signaling architecture. The immune ATP nucleosidase domain is also encoded within diverse eukaryotic proteins with immune-like architectures, and we show biochemically that eukaryotic homologs preserve the ATP nucleosidase activity. Our findings suggest that ATP and dATP degradation is a cell-autonomous innate immune strategy conserved across the tree of life.

Original languageEnglish
Pages (from-to)3619-3631.e13
Number of pages27
Issue number17
StatePublished - 17 Aug 2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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