Defence systems drive accessory genome interactions in Pseudomonas aeruginosa

As well as undergoing mutational selection, bacterial genomes are shaped by a complex evolutionary interplay among diverse accessory genome elements (AGEs). In this study we define AGEs as encompassing both autonomous elements including phage, plasmids, integrative conjugative elements (ICEs) and carried elements such as defence systems (DSs) and antimicrobial resistance genes (ARGs). Genomic studies can facilitate our better understanding of the relationships among these AGEs within microbial genomes, offering deeper insights into their roles in bacterial adaptation and evolution. Emerging evidence suggests that bacterial DSs can interact both synergistically and antagonistically with each other, and ecological studies describe non-random patterns of co-occurrence and avoidance of DSs in bacterial populations. Here, we analysed the distributions of DSs and other AGEs in a recently curated dataset of 4,288 Pseudomonas aeruginosa genomes. Genomic DS content varied by ecological niche, with higher numbers per genome in non-CF isolates (average n=7.9) compared to CF isolates (average n=6.9). We observed multiple phylogenetically independent associations (n=426) and dissociations (n=50) among DSs, and among other AGEs, many of which had a plausible biological basis. We further explored the relative importance of interactions among different AGEs, revealing that DSs and anti-defence systems engage in the most significant interactions with other AGEs and, most notably, with each other. Ultimately, these patterns of DS interactions and their variation across ecological niches reveals the evolutionary conflicts shaping bacterial accessory genomes and provides a significant public resource for downstream studies on DS and other AGE interactions.