Plasmid-dependent phages are bacterial viruses which unusually, instead of depending on chromosomally encoded receptors, use receptors encoded on conjugative plasmids. This gives them exceptionally broad host ranges, and movement of a conjugative plasmid through a bacterial community can rapidly create large pools of phage-susceptible bacteria. Plasmid-dependent phages also belong to unusual groups of non-tailed phages including Tectiviridae, Inoviridae and Fiersviridae. Despite their interesting biology and potentially profound effect on the ecology and evolution of horizontal gene transfer, technical challenges have impeded their study. We have developed a simple fluorescence-based method, phage DisCo (Discovery by Coculture) that allows us to systematically isolate phages that infect bacteria carrying specific conjugative plasmids.

In this talk, I will describe how we applied this method to isolate an unprecedented collection of novel plasmid-dependent phages. We discover that rather than being rare biological oddities, these bacteriophages are common and hugely under-sampled: the diversity we uncovered in Boston (USA) vastly expands the known global diversity, encompassing several putative novel species. Furthermore we find these phages are surprisingly absent from metagenomic datasets, hinting at the failure of metaviromics to capture them. Using high-throughput phenotypic profiling we find evidence for host range restriction amongst certain phage isolates, and we are actively exploring how both plasmids and bacteria defend themselves against plasmid-dependent phages.

The discovery of these diverse phage populations has important implications for horizontal gene transfer, and likely represents an unexplored, and potentially exploitable, force shaping the ecology and evolution of antibiotic resistance in bacteria.