Defence systems drive accessory genome interactions in Pseudomonas aeruginosa

Abstract Bacterial genomes represent dynamic ecological systems in which highly dynamic accessory genome element compositions drive evolution. Emerging evidence suggests that bacterial defence systems, which protect against phages and other genetic elements, can interact cooperatively, competitively, and antagonistically to influence horizontal gene transfer, shape phage susceptibility, and diversify genomes across environments. Recent ecological studies reveal non-random co-occurrence and avoidance patterns among defence systems suggesting that these patterns may emerge from ecological and evolutionary interactions rather than chance. Hence, these patterns need exploring in the context of ecological niche and co-localisation to identify putative functional compatibilities and elucidate how defence systems shape the accessory genome. To characterise these patterns, we analysed the distributions of defence systems and other accessory genome elements in a curated global dataset of 2940 Pseudomonas aeruginosa. Defence system content varied by ecological niche, with higher numbers in non-cystic fibrosis derived isolates (average n = 7.9) compared to cystic fibrosis-derived isolates (average n = 6.5). There were also multiple associations (n = 426) and dissociations (n = 50) among defence systems, and among other accessory genome elements, many with a plausible biological explanation. We also found that defence and anti-defence systems engage in more interactions than other accessory genome element types (e.g. antimicrobial resistance genes, plasmids) suggesting that they are a major driving force in the ecological dynamics of bacterial genomes. These patterns provide new insights into the evolutionary forces shaping bacteria, and provide a valuable resource of robustly quantitated interactions, establishing a baseline for future mechanistic and ecological investigations of defence system interactions.