Co-occurrence and synergism of anti-phage defence systems

Anti-phage defence systems in bacterial genomes show great diversity within and between species.

We examined whether combinations of defence systems are favoured or disfavoured based on their impact on anti-phage protection. By analysing the co-occurrence of defence systems in thousands of Escherichia coli genomes, we found that positive and negative co-occurring combinations are prevalent.

Surprisingly, our experimental findings demonstrate that both types of combinations can provide synergistic anti-phage activities, contingent on the specific phage being targeted.

Furthermore, we observed no consistent patterns of defence system co-occurrence across different bacterial taxa, hinting that the selection of strains carrying specific combinations of defence systems is driven by environmental pressures rather than mechanistic incompatibilities between these systems.

Using short-term evolution experiments, we observed that combinations of synergistic defence systems are preferentially selected in bacterial populations, regardless of the phage multiplicity of infection. However, this selection occurs only when these defence systems face pressure from phages against which they synergise.

Additionally, our characterisation of the synergy between two defence systems that positively co-occur at the molecular level revealed that a primary defence system co-opts a functional domain from a secondary system to enhance its effectiveness.

Overall, our study underscores the intricate interplay among anti-phage defence systems, and how these dynamics are influenced by specific phage pressures.

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