Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Nat Commun. 2024 Feb 22;15(1):1644. doi: 10.1038/s41467-024-45892-x.
Bacteria have evolved diverse antiviral defence mechanisms to protect themselves against phage infection. Phages integrated into bacterial chromosomes, known as prophages, also encode defences that protect the bacterial hosts in which they reside. Here, we identify a type of anti-phage defence that interferes with the virion assembly pathway of invading phages. The protein that mediates this defence, which we call Tab (for 'Tail assembly blocker'), is constitutively expressed from a Pseudomonas aeruginosa prophage. Tab allows the invading phage replication cycle to proceed, but blocks assembly of the phage tail, thus preventing formation of infectious virions. While the infected cell dies through the activity of the replicating phage lysis proteins, there is no release of infectious phage progeny, and the bacterial community is thereby protected from a phage epidemic. Prophages expressing Tab are not inhibited during their own lytic cycle because they express a counter-defence protein that interferes with Tab function. Thus, our work reveals an anti-phage defence that operates by blocking virion assembly, thereby both preventing formation of phage progeny and allowing destruction of the infected cell due to expression of phage lysis genes.
细菌已经进化出多种抗病毒防御机制来保护自己免受噬菌体感染。整合到细菌染色体上的噬菌体，称为原噬菌体，也编码防御机制来保护它们所在的细菌宿主。在这里，我们发现了一种干扰入侵噬菌体病毒组装途径的抗噬菌体防御机制。介导这种防御的蛋白质，我们称之为 Tab（Tail assembly blocker 的缩写），由铜绿假单胞菌的原噬菌体组成性表达。Tab 允许入侵噬菌体复制周期继续，但阻止噬菌体尾部的组装，从而阻止形成有感染性的病毒粒子。虽然感染细胞因复制噬菌体裂解蛋白的活性而死亡，但没有释放有感染性的噬菌体后代，因此细菌群落免受噬菌体流行的影响。表达 Tab 的原噬菌体在其自身的裂解周期中不会受到抑制，因为它们表达一种拮抗防御蛋白，干扰 Tab 的功能。因此，我们的工作揭示了一种通过阻断病毒粒子组装来发挥作用的抗噬菌体防御机制，从而既能阻止噬菌体后代的形成，又能因噬菌体裂解基因的表达而导致感染细胞的破坏。
