Native pathogen-phage networks reveal multilayered defense and gut-active anti-phage immunity.

Prophage-encoded AppA provides a novel anti-phage defense mechanism that suppresses phage expansion in the mammalian gut, influencing disease outcomes.

• Why it matters: Understanding how bacteria resist phage infection within native hosts is crucial for grasping pathogen evolution and infection dynamics, yet these mechanisms are not well characterized.
• What they did: The study mapped over 1,000 interactions between Salmonella isolates and wild phages, using genome-scale fitness profiling and genomics, and identified AppA as a prophage-encoded anti-phage factor.
• The result: AppA inhibits phage DNA packaging by mimicking a terminase interface, is expressed during mammalian infection, and reduces phage expansion in the murine gut, highlighting its role in in vivo bacterial defense.