Phage proteases activate CBASS antiphage immunity.

Phage prohead proteases activate CBASS immune pathways in bacteria, triggering antiviral defense through cleavage of CD-NTase activation loops in multiple clades.

• Why it matters: Understanding how bacteria detect and respond to phage infection is crucial for insights into microbial immunity and potential biotechnological applications. The mechanisms behind CBASS activation remained unclear, especially how late-stage infection signals initiate defense.
• What they did: The study reconstituted CBASS recognition of phage T4 in vitro and identified phage prohead protease activity as a key activator, demonstrating proteolytic cleavage of a CD-NTase activation loop as the trigger for immune signaling.
• The result: This discovery reveals a widespread antiviral strategy where phage proteases directly activate bacterial immunity, expanding knowledge of host-pathogen interactions and potential avenues for controlling bacterial infections.