A bacteriophage that evades immune nucleases by pretending to be a eukaryote

Bacteria use front-line defenses like CRISPR-Cas and restriction-modification (R-M) systems to rapidly cleave bacteriophage DNA. However, phages have evolved mechanisms to thwart these systems including anti-CRISPR proteins, anti-RM proteins, DNA modifications, and fascinating nucleus-like structures, necessitating a co-evolutionary response for the host for the host. Here, I will describe a jumbo phage infecting the human pathogen Pseudomonas aeruginosa that manifests a remarkable number of “eukaryote-like” complexities to avoid host nucleases. These features include a transcriptionally active endosome-like vesicle created immediately upon infection, a proteinaceous nucleus-like structure, microtubules that center the phage nucleus in the cell, and a protein sorting mechanism. These pathways ensure that the phage DNA is never exposed to the bacterial cytoplasm. We have additionally identified a novel, widespread, and specific defense system “jumbo phage killer” that detects and attacks the endosome-like structure, preventing production of the phage nucleus and saving the cell. In summary, this phage family has innovated sophisticated and fascinating biological mechanisms due to pressure from host nucleases, necessitating a tailored counter-response from the host.