Extended Data Fig. 9. Model of the molecular antagonism between Vs.4 and cGAS conjugation.

In response to phage infection, bacterial cGAS (purple) is activated and produces the second messenger cGAMP from ATP (red) and GTP (blue). cGAMP is bound by the phage encoded protein Vs.4 (orange), which acts as a cGAMP ‘sponge’ that sequesters cGAMP and prevents activation of the bacterial ‘suicide’ effector protein CapV. This allows the phage to propagate within the bacterial cell, as shown in the left panel. In contrast, when cGAS is conjugated to its biological target, enhanced cGAS activity produces abundant cGAMP that overpowers Vs.4 inhibition and activates the phospholipase activity of CapV. CapV activation disrupts the bacterial membrane and kills the bacterial cell before the phage replication cycle is complete, thereby preventing phage propagation.