Bacteria sense virus-induced genome degradation via methylated mononucleotides.

Abstract

Phages often degrade the genome of their bacterial host to individual nucleotides. Here we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis aborts phage infection once it detects the modified mono-nucleotide m⁶dAMP. As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m⁶dAMP signals that the host genome has been degraded. In type I Metis, sensing of m⁶dAMP activates an NAD⁺ diphosphatase, leading to NAD⁺ depletion and cessation of the infection process; while the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mono-nucleotide. We further show that Metis defense depends on endogenous DNA methylases, and that phages can escape Metis via mutations that inactivate host genome degradation.