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Peer-reviewedCC BYScience

Bacteria sense virus-induced genome degradation via methylated mononucleotides

4 affiliations
  1. 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
  2. 2Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
  3. 3Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel
  4. 4Protein Analysis Unit, Life Science Core Facility, Weizmann Institute of Science, Rehovot, Israel

Abstract

Phages often degrade the genome of their bacterial host to individual nucleotides. In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis aborts phage infection once it detects the modified mononucleotide N 6 -methyl-deoxyadenosine monophosphate (m 6 dAMP). As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m 6 dAMP signals that the host genome has been degraded. In type I Metis, sensing of m 6 dAMP activates a nicotinamide adenine dinucleotide (NAD + ) diphosphatase, leading to NAD + depletion and cessation of the infection process, whereas the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mononucleotide. We further show that Metis defense depends on endogenous DNA methylases and that phages can escape Metis through mutations that inactivate host genome degradation.

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BibTeX
@article{osterman2026bacteria,
  title = {{Bacteria sense virus-induced genome degradation via methylated mononucleotides}},
  author = {Ilya А. Osterman and Bohdana Hurieva and Sarit Moses and A. H. Falkovich and Maxim Itkin and Sergey Malitsky and Eliane Hadas Yardeni and Erez Yirmiya and Rotem Sorek},
  journal = {Science},
  year = {2026},
  month = jul,
  doi = {10.1126/science.aed6782},
  url = {https://doi.org/10.1126/science.aed6782},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Bacteria sense virus-induced genome degradation via methylated mononucleotides
AU  - Ilya А. Osterman
AU  - Bohdana Hurieva
AU  - Sarit Moses
AU  - A. H. Falkovich
AU  - Maxim Itkin
AU  - Sergey Malitsky
AU  - Eliane Hadas Yardeni
AU  - Erez Yirmiya
AU  - Rotem Sorek
PY  - 2026
DA  - 2026/07/09
JO  - Science
DO  - 10.1126/science.aed6782
UR  - https://doi.org/10.1126/science.aed6782
AB  - Phages often degrade the genome of their bacterial host to individual nucleotides. In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis aborts phage infection once it detects the modified mononucleotide N 6 -methyl-deoxyadenosine monophosphate (m 6 dAMP). As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m 6 dAMP signals that the host genome has been degraded. In type I Metis, sensing of m 6 dAMP activates a nicotinamide adenine dinucleotide (NAD + ) diphosphatase, leading to NAD + depletion and cessation of the infection process, whereas the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mononucleotide. We further show that Metis defense depends on endogenous DNA methylases and that phages can escape Metis through mutations that inactivate host genome degradation.
SN  - 0036-8075
SN  - 0193-4511
SN  - 1095-9203
ER  -