Targeted phage metagenomics

Bacteriophages are the most abundant biological entities on Earth, with an estimated 10^31 in the biosphere. They drive bacterial evolution by mediating horizontal gene transfer, spreading antimicrobial resistance and virulence genes. Despite their abundance, their diversity has only recently been explored through culture-independent methods like viral metagenomics. However, metagenomics alone cannot link phages to their hosts. Traditionally, host range is determined using plaque assays, which visualise plaques if a phage causes productive infection. Yet, this method has limitations: temperate phages do not form plaques, and some phages attach and inject DNA without replicating due to host defences. Understanding which hosts phages infect and transfer genes between is crucial for studying bacterial evolution and optimising phage therapy or phage-based delivery systems. This study explores whether bacterial minicells can selectively isolate host-specific phages from complex natural communities. Minicells are chromosome-free bacterial derivatives that retain membrane receptors for phage attachment. We hypothesise that only host-specific phages will infect minicells, allowing unbound phages to be washed away. Combined with metagenomics, this approach could directly link phages to hosts, revolutionising phage metagenomics.