Future prospects of structural studies to advance our understanding of phage biology

Bacteriophages, being the most abundant biological entities on the Earth, play a major role in regulating populations of bacteria and thus influence the evolution and stability of ecosystems. Phage infections of pathogenic bacteria can both exacerbate and alleviate the severity of the disease. The structural characterisations of phage particles and individual proteins have enabled the understanding of many aspects of phage biology. Due to methodological limitations, most of the structures were determined from purified samples in vitro. However, studies performed outside the cellular context cannot capture the complex and dynamic interactions of the macromolecules that are required for their biological functions. Current developments in structural biology, in particular cryo-electron microscopy, allow in situ high-resolution studies of phage-infected cells. Here we discuss open questions in phage biology that could be addressed by structural biology techniques and their potential to enable the use of tailed phages in industrial applications and human therapy.