Synergistic anti-phage activity of bacterial defence systems

Wu, Yi; Hurk, Anne van den; Aparicio-Maldonado, Cristian; Kushwaha, Simran Krishnakant; King, Claire; Todeschini, Thomas C; Clokie, Martha R. J.; Millard, Andrew; Gençay, Yılmaz Emre; Nóbrega, Franklin L.

doi:10.1101/2022.08.21.504612

Cited by 16 publications

(16 citation statements)

References 112 publications

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“…1). Notably, each serovar appears to have a distinct profile of defence systems, suggesting selection of the most beneficial systems in specific environments or host interactions, as previously observed for distinct E. coli phylogroups 44 . For example, in serovars Typhi and Paratyphi A, the 3HP and Druantia type III systems are highly abundant.…”

Section: Anti-phage Defence Systems Are More Prevalent In Chromosomal...supporting

confidence: 53%

Genomic plasticity is a blueprint of diversity inSalmonellalineages

Kushwaha,

Anand,

et al. 2023

Preprint

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The flexible genome, organised in regions of genomic plasticity (RGP), serves as a potent facilitator of the dynamic evolution of bacterial genomes through gene acquisition and loss. Here we explored the genomic plasticity acrossSalmonellalineages, revealing a purposeful, non-random integration pattern of pathogenicity-related gene clusters into specific RGP. Noteworthy examples include the correlation between the type I-E CRISPR-Cas system, gold tolerance, and specific RGP. The scattered prevalence of RGP acrossSalmonellalineages profoundly shapes the pathogenicity makeup ofSalmonellastrains. The preferences of RGP seem guided by conserved flanking genes that likely share regulatory and functional coordination. For example, metal resistance genes are predominant in RGP positioned near stress resistance genes, indicating a regulatory network to efficiently counter stressors. Additionally, we observed that different plasmid incompatibility types and prophage genera carry distinct pathogenicity genes. Similar to RGP, their distribution acrossSalmonellalineages plays a critical role in defining pathogenicity. By uncovering these intricate connections among gene clusters, RGP, mobile genetic elements, and pathogenic attributes, our study offers novel insights into the evolutionary trajectory ofSalmonellaand holds promise for predicting future adaptations and developing targeted interventions against infections.

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Section: Anti-phage Defence Systems Are More Prevalent In Chromosomal...supporting

confidence: 53%

Genomic plasticity is a blueprint of diversity inSalmonellalineages

Kushwaha,

Anand,

et al. 2023

Preprint

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“…Our findings demonstrate the significance of the individual defense systems in predicting the susceptibility of P. aeruginosa strains to phages. However, factors such as genetic context, interactions among defense systems (49,(51)(52)(53), the presence of unknown defense systems, and anti-defense mechanisms will affect the final outcome of phage infection. Further research is required to enhance the predictive accuracy of genomic analysis, which could prove beneficial for ecological and evolutionary studies.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of defense systems in phage-resistant strains of Pseudomonas aeruginosa

Costa,

van den Berg,

Esser

et al. 2024

Sci. Adv.

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Prokaryotes encode multiple distinct anti-phage defense systems in their genomes. However, the impact of carrying a multitude of defense systems on phage resistance remains unclear, especially in a clinical context. Using a collection of antibiotic-resistant clinical strains of Pseudomonas aeruginosa and a broad panel of phages, we demonstrate that defense systems contribute substantially to defining phage host range and that overall phage resistance scales with the number of defense systems in the bacterial genome. We show that many individual defense systems target specific phage genera and that defense systems with complementary phage specificities co-occur in P. aeruginosa genomes likely to provide benefits in phage-diverse environments. Overall, we show that phage-resistant phenotypes of P. aeruginosa with at least 19 phage defense systems exist in the populations of clinical, antibiotic-resistant P. aeruginosa strains.

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“…It is likely that this aggregation of defense systems within mobile elements provides fitness benefits to recipient bacteria living in a phage-rich environment [1]. It has also been suggested that synergism between defense systems may promote their co-localization within and co-transfer between genomes [22,46,47]. Genes involved in bacterial pathogenicity are frequently mobilized between bacteria on "pathogenicity islands", which constitute MGEs carrying clusters of pathogenicity genes [48].…”

Section: Plos Geneticsmentioning

confidence: 99%

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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Synergistic anti-phage activity of bacterial defence systems

Cited by 16 publications

References 112 publications

Genomic plasticity is a blueprint of diversity inSalmonellalineages

Genomic plasticity is a blueprint of diversity inSalmonellalineages

Accumulation of defense systems in phage-resistant strains of Pseudomonas aeruginosa

The defense island repertoire of the Escherichia coli pan-genome

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