Phages and their satellites encode hotspots of antiviral systems

Bacteria carry diverse genetic systems to defend against viral infection, some of which are found within prophages where they inhibit competing viruses. Phage satellites pose additional pressures on phages by hijacking key viral elements to their own benefit. Here, we show that E. coli P2-like phages and their parasitic P4-like satellites carry hotspots of genetic variation containing reservoirs of anti-phage systems. We validate the activity of diverse systems and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Antiviral hotspots participate in inter-viral competition and shape dynamics between the bacterial host, P2-like phages, and P4-like satellites. Notably, the anti-phage activity of satellites can benefit the helper phage during competition with virulent phages, turning a parasitic relationship into a mutualistic one. Anti-phage hotspots are present across distant species and constitute a substantial source of systems that participate in the competition between mobile genetic elements. [Display omitted] •P2 phages and P4 satellites carry a genetic hotspot of diverse anti-phage systems•The PARIS system kills the host in the presence of a phage anti-restriction protein•Satellites are parasites of phages, but anti-phage systems can make them mutualistic•Hotspots of anti-phage systems are found in prophages of diverse species Rousset, Depardieu et al. show that E. coli P2-like phages and their parasitic P4-like satellites carry diverse anti-phage systems. The PARIS system induces abortive infection, triggered by a phage-encoded anti-restriction protein. Anti-phage systems can turn the parasitic satellite-phage relationship into a mutualistic one when facing a common threat.