Discovering New Jumbo Phage Biology with Cryo–Electron Microscopy

Phages invade and replicate in bacteria, resulting in host cell death. In our review, we highlight the impact of electron microscopy on phage research. Recent advances in the field of cryo–electron microscopy, including single-particle analysis, focused ion beam milling, and cryo–electron tomography, play a crucial role in understanding the structure and mechanisms involved in phage replication. Here we focus on jumbo phages, characterized by a large ∼200-kb genome, many of which belong to the new Chimalliviridae family whose genome encodes for a unique replication cycle. Upon phage genome injection into the host cell, the DNA is surrounded by an early phage injection (EPI) vesicle that serves as a hub for initial synthesis of early phage proteins. One of these early proteins, chimallin, forms a nucleus that replaces the EPI vesicle and continues to protect the replicating phage DNA against the host defense systems.