The complex developmental mechanisms of nucleus-forming jumbo phages

Bacteriophages related to the jumbo phage ΦKZ (Family: Chimalliviridae) exhibit a complex developmental cycle. First, two large macromolecular compartments are assembled that surround and protect the bacteriophage genome. Upon infection, the injected phage genomic DNA (gDNA) is rapidly enclosed within a lipid-based 'early phage infection (EPI) vesicle', assembled with bacterial membrane components and injected phage proteins. The EPI vesicle serves as a hub for early transcription and localized protein synthesis. One early-expressed protein, Chimallin A (ChmA)/Phage Nuclear Enclosure (PhuN), assembles a distinct proteinaceous 'phage nucleus' that receives the phage gDNA from the EPI vesicle. Within this phage nucleus, phage DNA is replicated and transcribed by selectively imported phage and host enzymes. The EPI vesicle, phage nucleus, and packaged capsid completely isolate the phage gDNA from nucleases in the bacterial cytoplasm. Here, we review the complex jumbo phage infection cycle, anti-immune strategies, their respective roles in supporting infection, and recent tools used to dissect these intricate processes.