An Lsr2-like xenogeneic silencer confers immunity against AT-rich bacteriophage infection

Lsr2-like xenogeneic silencers are widespread nucleoid-associated proteins in Actinomycetota and are encoded by diverse bacteriophages. However, their roles during bacteriophage infection, one of the most direct encounters with foreign DNA, remain unexplored. In Corynebacterium glutamicum, the Lsr2-like protein CgpS is encoded within the mobile genetic element CGP3 and is known to silence transcription of foreign DNA within this region. Here we show that CgpS restricts infection by the AT-rich bacteriophage JeanGrey. Upon phage DNA injection, CgpS binds phage-derived AT-rich sequences and represses early phage gene transcription. This transcriptional bottleneck prevents efficient phage genome replication and delays progression of the viral program. The resulting temporal window enables activation of host stress and defense pathways, including LexA-regulated SOS genes and antiviral systems. Our findings reveal a novel antiviral function for an Lsr2-like silencer and suggest that xenogeneic silencers can act as regulatory barriers that modulate the outcome of phage infection in Actinomycetota.