22 February 2024 | Pramalkumar H. Patel, Véronique L. Taylor, Chi Zhang, Landon J. Getz, Alexa D. Fitzpatrick, Alan R. Davidson, Karen L. Maxwell
Bacteria have evolved various antiviral defense mechanisms to protect themselves against phage infection. This study identifies a novel anti-phage defense mechanism in *Pseudomonas aeruginosa* that inhibits the assembly of invading phage virions. The protein, named Tab (Tail assembly blocker), is constitutively expressed from a prophage and blocks the assembly of phage tails, preventing the formation of infectious virions. While the infected cell dies due to the activity of the phage's lysis genes, there is no release of infectious phage progeny, thus protecting the bacterial community from a phage epidemic. Prophages expressing Tab also possess a counter-defence protein, anti-Tab, which interferes with Tab function during their own lytic cycle. This work reveals a new archetype of anti-phage defense that directly targets and inhibits the virion assembly pathway.Bacteria have evolved various antiviral defense mechanisms to protect themselves against phage infection. This study identifies a novel anti-phage defense mechanism in *Pseudomonas aeruginosa* that inhibits the assembly of invading phage virions. The protein, named Tab (Tail assembly blocker), is constitutively expressed from a prophage and blocks the assembly of phage tails, preventing the formation of infectious virions. While the infected cell dies due to the activity of the phage's lysis genes, there is no release of infectious phage progeny, thus protecting the bacterial community from a phage epidemic. Prophages expressing Tab also possess a counter-defence protein, anti-Tab, which interferes with Tab function during their own lytic cycle. This work reveals a new archetype of anti-phage defense that directly targets and inhibits the virion assembly pathway.