A prophage-encoded anti-phage defence system that prevents DNA packaging by targeting the terminase complex

A common feature of temperate phages is their ability to protect their host bacteria from a second phage infection. This protection occurs during the lysogenic state, when the phages remain as prophages integrated into the bacterial chromosome and express genes that defend both the host and themselves against predation. Here, we report a prophage-encoded anti-phage defence system that inhibits DNA packaging of invading phages in Listeria monocytogenes. This system includes a defence protein, TerI, and two self-immunity proteins, anti-TerI1 and anti-TerI2. TerI targets the terminase complex of invading phages to prevent DNA translocation into procapsids, without halting the lytic cycle, thereby releasing unpacked, non-infectious procapsids upon bacterial lysis. Conversely, the self-immunity proteins, anti-TerI1 and anti-TerI2, counteract TerI during prophage induction, thereby facilitating virion production. We found that the prophage-encoded anti-phage defence system, TERi, is common in Listeria phages, offering population-level host protection without compromising the prophage’s lytic lifecycle. Some temperate phages protect their host bacteria from a second phage infection. Here, the authors show that a prophage encodes an anti-phage defence system, which inhibits packaging of invading phage DNA, and self-immunity proteins that enable the resident prophage to propagate