The defence island repertoire of the Escherichia coli pan-genome

Abstract

In recent years it has become clear that anti-phage defence systems cluster non-randomly within bacterial genomes in so-called "defence islands". Despite serving as a valuable tool for the discovery of novel defence systems, the nature and distribution of defence islands themselves remain poorly understood. In this study, we comprehensively mapped the repertoire of defence islands within >1,300 strains of Escherichia coli, the most widely studied organism in terms of phage-bacteria interactions. We found that defence islands preferentially integrate at several dozens of dedicated integration hotspots in the E. coli genome. Defence islands are usually carried on mobile genetic elements including prophages, integrative conjugative elements and transposons, as well as on other genetic elements whose nature of mobilisation is unclear. Each type of mobile genetic element has a preferred integration position but can carry a diverse variety of defensive cargo. On average, an E. coli genome has 4.5 genomic hotspots occupied by a defence system-containing mobile element, with some strains possessing up to eight defensively occupied hotspots. Our data show that the overwhelming majority of the E. coli pan-immune system is carried on mobile genetic elements that integrate at a discrete set of genomic hotspots, and explains why the immune repertoire substantially varies between different strains of the same species.

Shield co-opts an RmuC domain to mediate phage defence acrossPseudomonasspecies

“…They also often associate with WYL-domain containing proteins, transcriptional regulators that are enriched in phage defense islands (3,30,31). Furthermore, the genome neighborhood also encodes several viral proteins and integrases, in agreement with recent reports that mobile genetic elements (MGE) represent primary carriers of defense islands (14,26,32). These findings further support the involvement of the Shield systems in bacterial immunity.…”

Core Defense Hotspots withinPseudomonas aeruginosaare a consistent and rich source of anti-phage defense systems

“…The current explosion anti-phage immune systems discovered in bacterial genomes has prompted the analysis their genomic positioning. Fascinating examples of MGE transferred hotspots of anti-phage immunity have been documented that control ecological outcomes during phage-host interactions in Vibrio and E. coli, for example (7)(8)(9)(29)(30)(31). In contrast to these phage defense MGEs, however, here we show that core defense hotspots (cDHS) with conserved genomic markers flanking immunity regions can be predictive of an immune locus.…”

“…In contrast, cDHS regions in Pseudomonas aeruginosa we sporadically identified mobilizing genes (e.g., transposases), the regions have a large size variance across the isolates, and we observe distant isolates carrying almost identical DNA between the cDHS flanking regions with the gain/loss of an anti-phage MGE (Figure 7C). In contrast, the elements present at 41 mDHS sites described in E. coli) typically belong to a single mobile genetic element family and their presence is hypervariable (i.e., each locus is occupied in 8% of isolates on average) (31). These are signatures of a landing spot for a specific MGE.…”

Synergistic anti-phage activity of bacterial defence systems

“…In recent years, dozens of new anti-phage defence systems were discovered based on the observation that defences are commonly located in defence islands in the bacterial genome (Doron et al, 2018; Gao et al, 2020; Makarova et al, 2013; Millman et al, 2022; Rousset et al, 2022; Vassallo et al, 2022). These genomic islands have been suggested to facilitate mobilization of the defence systems between bacterial strains and are usually of variable composition (Hochhauser et al, 2022; Piel et al, 2022; Tesson et al, 2022). Evidence suggests that certain sets of defence systems seem to be more conserved than others (Costa et al, 2022), suggesting that specific combinations of defence systems may co-occur in bacterial genomes for enhanced anti-phage defence.…”