Core Defense Hotspots within<i>Pseudomonas aeruginosa</i>are a consistent and rich source of anti-phage defense systems

Johnson, Matthew C; Laderman, Eric; Huiting, Erin; Zhang, Charles; Davidson, Alan R.; Bondy‐Denomy, Joseph

doi:10.1101/2022.11.11.516204

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…In contrast, hotspot #37 was highly occupied, with diverse defense systems present in almost all genomes in which it was detected. This position seems to represent a dedicated defense hotspot that may play a role in promoting defense system diversity within the E. coli pan-genome, as was also observed in strains of P. aeruginosa [39].…”

Section: Plos Geneticsmentioning

confidence: 53%

“…While in some cases hotspot #37 contained prophages, P4-type phage satellites or IMEs, the majority (68.0%) of mobile islands carrying defense systems at this hotspot did not have any detectable MGEs, although many contained integrase or recombinase genes (Fig 6 and S2 Table). Notably, a recent study showed that Pseudomonas aeruginosa genomes encode two highly diverse hotspots that seem to be similarly dedicated to carrying defense systems, with some cases showing no identifiable modes of mobilization [39].…”

Section: Plos Geneticsmentioning

confidence: 99%

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The defense island repertoire of the Escherichia coli pan-genome

2023

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It has become clear in recent years that anti-phage defense systems cluster non-randomly within bacterial genomes in so-called “defense islands”. Despite serving as a valuable tool for the discovery of novel defense systems, the nature and distribution of defense islands themselves remain poorly understood. In this study, we comprehensively mapped the defense system repertoire of >1,300 strains of Escherichia coli, the most widely studied organism for phage-bacteria interactions. We found that defense systems are usually carried on mobile genetic elements including prophages, integrative conjugative elements and transposons, which preferentially integrate at several dozens of dedicated hotspots in the E. coli genome. Each mobile genetic element type has a preferred integration position but can carry a diverse variety of defensive cargo. On average, an E. coli genome has 4.7 hotspots occupied by defense system-containing mobile elements, with some strains possessing up to eight defensively occupied hotspots. Defense systems frequently co-localize with other systems on the same mobile genetic element, in agreement with the observed defense island phenomenon. Our data show that the overwhelming majority of the E. coli pan-immune system is carried on mobile genetic elements, explaining why the immune repertoire varies substantially between different strains of the same species.

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Section: Plos Geneticsmentioning

confidence: 53%

Section: Plos Geneticsmentioning

confidence: 99%

The defense island repertoire of the Escherichia coli pan-genome

2023

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“…In addition, these MGE tend to integrate at preferential locations in bacterial genomes, known as integration hotspots. Therefore, systematic mapping of integration hotspots and careful analyses of their gene content is becoming a valuable strategy for the discovery of the full repertoire of bacterial defence systems [40][41][42][43] . We now understand that bacteria encode many more defence systems than previously thought, and that individual bacterial genomes typically contain multiple defences.…”

Section: Discussionmentioning

confidence: 99%

Bacterial defences interact synergistically by disrupting phage cooperation

Maestri

Pursey

Chong

et al. 2023

Preprint

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The constant arms race between bacteria and their phages has resulted in a large diversity of bacterial defence systems, with many bacteria carrying several systems. In response, phages often carry counter-defence genes. If and how bacterial defence mechanisms interact to protect against phages with counter-defence genes remains unclear. Here, we report the existence of a novel defence system, coined MADS (Methylation Associated Defence System), which is located in a strongly conserved genomic defence hotspot in Pseudomonas aeruginosa and distributed across Gram-positive and Gram-negative bacteria. We find that the natural co-existence of MADS and a Type IE CRISPR-Cas adaptive immune system in the genome of P. aeruginosa SMC4386 provides synergistic levels of protection against phage DMS3, which carries an anti-CRISPR (acr) gene. Previous work has demonstrated that Acr-phages need to cooperate to overcome CRISPR immunity, with a first sacrificial phage causing host immunosuppression to enable successful secondary phage infections. Modelling and experiments show that the co-existence of MADS and CRISPR-Cas provides strong and durable protection against Acr-phages by disrupting their cooperation and limiting the spread of mutants that overcome MADS. These data reveal that combining bacterial defences can robustly neutralise phage with counter-defence genes, even if each defence on its own can be readily by-passed, which is key to understanding how selection acts on defence combinations and their coevolutionary consequences.

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“…Computational prediction of the presence or absence of various defense systems in ECOR strains used in the PhAGENT screen. Predictions were generated using the ISLAND software suite 57 .…”

Section: Supplementary Figure 1 Phage-host Combinations Included In P...mentioning

confidence: 99%

Activation of programmed cell death and counter-defense functions of phage accessory genes

Silas

Carion

Makarova

et al. 2023

Preprint

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Genomes of bacterial and archaeal viruses are replete with fast-evolving, uncharacterized accessory genes (AGs), most of which likely antagonize host defenses or other viruses. We developed a computational pipeline to find AGs in bacteriophage genomes and built a high-throughput screening platform to assay their functions. This approach is targeted towards identifying the most salient antiviral mechanisms in any bacterial niche. We tested 200 Enterobacteriophage AGs in 20 wild Escherichia coli strains challenged with 8 phages. The most prominent AG functions we observed were antagonism of O-antigen-based barrier defense and restriction-modification (R-M) systems. In response to phage-encoded anti-R-M strategies, some Type I and III R-M systems surprisingly act as programmed-cell-death modules. Moreover, several hyper-variable AGs trigger other abortive defense systems, demonstrating that phage-associated molecular patterns that activate immunity need not be well-conserved. Our approach yields insights into the multiple levels of virus-host competition and can be rapidly deployed in various bacteria.

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

Cited by 7 publications

References 38 publications

The defense island repertoire of the Escherichia coli pan-genome

The defense island repertoire of the Escherichia coli pan-genome

Bacterial defences interact synergistically by disrupting phage cooperation

Activation of programmed cell death and counter-defense functions of phage accessory genes

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