The study examines bacterial antiviral defense systems and describes the repeated acquisition of gene pairs that encode a nuclease and a trypsin-like protease.[1][3] The authors found that the nuclease is first in an inactive (proenzyme) form and begins to cleave DNA only after activation by a coupled protease.[1][3] Cellular and biochemical experiments have confirmed that this mechanism leads to antiviral defenses by disrupting viral or cellular DNA upon activation.[1][4] Two independent bacterial immune systems, Hachiman and AVAST (Avs), use the same principle of proteolytic activation despite different evolutionary origins.[1][3] Phylogenetic analysis of the inheritance of these pairs showed that similar nuclease-protease modules are repeatedly integrated into different immune systems during evolution.[2][4] The authors also identified genomic loci called caspase‑nuclease (canu) that mediate antiviral defense in a manner reminiscent of caspase activation in eukaryotes.[1][2] The results show the coordinated activity of "pro-nucleases" and their activating proteases in different bacterial immune systems and document how their coevolution contributes to the innovation of defense mechanisms against viruses.[1][3]