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bioRxiv · 10.1101/2024.10.24.620036

TIR signaling activates caspase-like immunity in bacteria

ROUSSET, F.·Osterman, I.·Scherf, T.·Falkovich, A.·Leavitt, A.·Amitai, G.·Shir, S.·Malitsky, S.·Itkin, M.·Savidor, A.·Sorek, R.
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Abstract

Proteases of the caspase family, as well as Toll/Interleukin-1 Receptor (TIR)-domain proteins, have central roles in innate immunity and regulated cell death in humans. In this study we describe a bacterial immune system comprising both a caspase-like protease and a TIR-domain protein. We found that the TIR protein, once it recognizes phage invasion, produces the previously unknown immune signaling molecule ADP-cyclo[N7:1'']-ribose (N7-cADPR). This molecule specifically activates the bacterial caspase-like protease which then indiscriminately degrades cellular proteins to halt phage replication. The TIR-caspase defense system, which we denote as type IV Thoeris, is abundant in bacteria and efficiently protects against phage propagation. Our study highlights the diversity of TIR-produced immune signaling molecules and demonstrates that cell death regulated by proteases of the caspase family is an ancient mechanism of innate immunity.

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ROUSSET, F., Osterman, I., Scherf, T., Falkovich, A., Leavitt, A., Amitai, G., Shir, S., Malitsky, S., Itkin, M., Savidor, A., Sorek, R.. 2024-10-25. TIR signaling activates caspase-like immunity in bacteria. https://doi.org/10.1101/2024.10.24.620036

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