A prophage-encoded abortive infection protein preserves host and prophage spread

Most bacterial pathogens are polylysogens, harbouring multiple vertically transmitted prophages1–3. These prophages enhance bacterial pathogenicity and survival by encoding virulence factors and anti-phage defence systems while retaining the capacity for horizontal transfer. Thus, prophage-encoded anti-phage defences must block propagation of external phages without inhibiting the spread of the prophages that encode them. Here we identify HepS—an abortive infection system encoded on the Gifsy-1 prophage constituted of a single HEPN domain protein—which restricts phages of the Siphoviridae family. We demonstrate that in its native host context of Salmonella enterica serovar Typhimurium, HepS both senses phage…