Bacteria sense virus-induced genome degradation via methylated mononucleotides.

Bacteria have developed a defense system called Metis that senses phage-induced genome degradation, potentially halting infection through NAD+ depletion.

Summary and findings

This study investigates the bacterial defense system Metis, which senses phage-induced genome degradation via the modified nucleotide m6dAMP. The research highlights how Metis activates an NAD+ diphosphatase, leading to NAD+ depletion and halting phage infection. No therapeutic claims are made.

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.

Key findings

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Limitations

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Elsewhere in the NAD+ (Nicotinamide Adenine Dinucleotide) corpus