Osterman Ilya: Bacteria can sense when a virus starts…

Phages often degrade host DNA into individual nucleotides to reuse them for building their own genomes. When this happens, bacterial cells are doomed — but not necessarily defenseless.

Ответ для Osterman Ilya

Osterman Ilya

6 нояб., 07:59

We found that bacteria can detect the degradation of their own genome — a hallmark of phage infection. They do it by sensing the accumulation of a modified nucleotide, N⁶-methyl-deoxyadenosine monophosphate (m⁶dAMP) — a signature molecule that appears when bacterial DNA is broken down.

Ответ для Osterman Ilya

Osterman Ilya

6 нояб., 07:59

In this work, we identified a two-gene anti-phage defense system, which we named Metis. Upon accumulation of m⁶dAMP, MisA is activated and rapidly depletes NAD⁺, shutting down the cell and preventing phage replication.

Ответ для Osterman Ilya

Osterman Ilya

6 нояб., 07:59

We also found that MisA cuts NAD⁺ in a unique way, producing NMN and AMP — unlike any previously known NAD⁺-depleting defense enzymes. This might prevent phages from rebuilding NAD⁺ through their usual repair pathways (for example, NARP1 - www.nature.com/articles/s41...).

Ответ для Osterman Ilya

Osterman Ilya

6 нояб., 07:59

The second gene, MisB, is an m⁶dAMP phosphatase. Low levels of m⁶dAMP can appear even without phage infection, during normal DNA repair. MisB “cleans” these traces to prevent premature activation and self-toxicity.

Ответ для Osterman Ilya

Osterman Ilya

6 нояб., 07:59

Metis doesn’t recognize a specific phage protein — it recognizes a consequence of infection: genome degradation. Phages can escape Metis by avoiding host DNA degradation (for example, through mutation of the DenA endonuclease), but that escape comes at a cost —they lose access to host nucleotides.

Ответ для Osterman Ilya

Osterman Ilya

6 нояб., 07:59

In many bacteria, MisB pairs not with MisA but with MisC, a protein with three transmembrane helices. Together, they form type II Metis — a defense system also activated by m⁶dAMP. AF3 predictions suggest that MisC could assemble into an octameric pore across the membrane during activation.

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Osterman Ilya

6 нояб., 07:59

Notably, an operon encoding homologs of MisC and MisB was previously shown to defend against phage T7 🔗 linkinghub.elsevier.com/retrieve/pii/S1931-3128(22)00104-4 @francoisrousset.bsky.social @dbikard.bsky.social

Ответ для Osterman Ilya

Osterman Ilya

6 нояб., 07:59

We call this new system Metis, after Greek Titaness of wisdom and deep thought — and fittingly, it’s a wise defender that knows when Methylation becomes a problem A molecular sensor that detects when the cell’s own DNA has been broken down.

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Osterman Ilya

6 нояб., 07:59

Huge thanks to Rotem Sorek and everyone in the @soreklab.bsky.social — especially @bhurieva.bsky.social and @erezyirmiya.bsky.social. Also to A. Falkovich, M. Itkin, and S. Malitsky. And special thanks to the very talented Weizmann student Sarit Moses, who started this project during her rotation.