Bacterial defence in a world of mobile genetic elements

Bacteria have evolved hundreds of specialised defence systems to protect themselves against mobile genetic elements (MGEs), including bacteriophages and plasmids. Yet bacterial immunity is inherently multilayered: cells often carry multiple defence systems alongside prophages, plasmids and other MGEs, creating complex interactions that can shape the outcome of infection.

As part of the MultiDefence consortium, we use Pseudomonas aeruginosa to investigate this complexity. To experimentally disentangle different layers of defence, we developed viPAO1, a genetically simplified strain lacking known defence systems, prophages and plasmids, together with a diverse collection of temperate and lytic phages. This platform allows us to introduce individual defence systems, prophages and their combinations into a common genetic background and directly compare their effects.

Combining this approach with comparative genomics, we investigate how different defence systems function, how prophages contribute to host defence while also encoding offensive traits, and how prophage genomic hotspots harbour novel defence and anti-defence mechanisms. By reconstructing combinations of defence systems and MGEs, we can further explore how these elements interact and modify one another’s phenotypes. Together, this work aims to understand bacterial immunity not as a collection of isolated defence systems, but as a dynamic network of interactions between bacteria and their mobile genetic elements.