Proteomic Analysis of Marine Bacteriophages: Structural Conservation, Post-Translational Modifications, and Phage–Host Interactions

Marine bacteriophages, the most abundant biological entities in marine ecosystems, are essential in biogeochemical cycling. Despite extensive genomic data, many phage genes remain uncharacterised, creating a gap between genomic diversity and gene function knowledge. This gap limits our understanding of phage life cycles, assembly, and host interactions. In this study, we used mass spectrometry to profile the proteomes of 13 marine phages from diverse lifestyles and hosts. The analysis accurately annotated hypothetical genes, mapped virion protein arrangements, and revealed structural similarities among phages infecting the same host, particularly in tail fibre proteins. Protein structure comparisons showed conservation and variability in head and tail proteins, particularly in key domains involved in virion stabilisation and host recognition. For the first time, we identified post-translational modifications (PTMs) in marine phage proteins, which may enhance phage adaptability and help evade host immune systems. These findings suggest that phages optimise their infection strategies through structural variations and PTM modifications, improving their adaptability and host interactions.