Molecular choreography of phage defence: sensing viral assembly to abort infection

The viruses that infect bacteria, known as bacteriophages or phages, have evolved alongside a vast repertoire of bacterial defence systems that collectively define the microbial immune landscape. The enormous genetic diversity presented by phages raises a central question of how these systems detect the presence of an infecting phage. We discovered a class of bacterial defence proteins that sense the molecular choreography of viral assembly, detecting oligomeric intermediates of phage structural proteins to trigger abortive infection. Using biochemical, structural, and genetic approaches, we show that this mechanism couples real-time surveillance of phage virion assembly with rapid host self-sacrifice, effectively halting viral propagation. By targeting a conserved and obligate step in the phage life cycle, this strategy not only disrupts virion assembly but is also intrinsically resistant to escape mutations. This work expands the conceptual boundaries of antiphage defence recognition and highlights evolutionary convergence between bacterial and eukaryotic immune strategies that detect the molecular signatures of infection.