Defence systems provide synergistic anti-phage activity in E. coli

Anti-phage defence systems in bacterial genomes have a vast intra- and inter-species diversity. Here we investigated whether combinations of defence systems are selected for or against due to the effects of anti-phage protection. Analysis of defence system co-occurrence in Escherichia coli genomes revealed that positive and negative co-occurrences are common, and surprisingly both can provide synergistic anti-phage activities. Furthermore, we did not find conserved patterns of defence system co-occurrence across bacterial taxa. This suggests that the selection of strains carrying defence system combinations is more likely a consequence of environmental conditions than mechanistic incompatibilities between defence systems. Additionally, we showed that Gabija and Zorya type II can sense the anti-restriction protein Ocr to activate defence, and that phages also make use of these shared sensing mechanisms to evade multiple defence systems with a single escape strategy. Together, our results highlight the complex co-evolutionary dynamics of phage defence and anti-defence. ### Competing Interest Statement Y.E.G. is a full-time employee of SNIPR Biome.