Bacteriophages antagonize cGAS-like immunity in bacteria

Huiting, Erin; Athukoralage, Januka S; Guan, Jingwen; Silas, Sukrit; Carion, Héloïse; Bondy‐Denomy, Joseph

doi:10.1101/2022.03.30.486325

Cited by 17 publications

(23 citation statements)

References 33 publications

(48 reference statements)

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“…One has to keep in mind that small ORFs in bacteriophages can encode small proteins enabling phages to evade host anti-phage systems. Among them are found: anti-CRISPR proteins (Acr) such as ACR3112-12 (52 aa) from Pseudomonas phage D3112 [52]; proteins preventing superinfection such as the immunity protein Imm (83 aa) of bacteriophage T4 [53] or the lipoprotein Llp (77aa) of bacteriophage T5 [54]; anti-RM proteins such as Ocr (117 aa) of bacteriophage T7 [55]; the newly discovered anti-CBASS Acb (about 94 aa) found in an increasing number of phages of various phylogenetic background such as Pseudomonas phages PaMx33, 35, 41 and 43 as well as the enterobacteriophage T4 [19, 20].…”

Section: Resultsmentioning

confidence: 99%

“…Undoubtedly, co-evolution works both ways, and phages therefore evolved their own arsenal to counter cellular defenses. One can cite anti-RM or anti-CRISPR proteins [18] as well as the newly discovered anti-CBASS and anti-Pycsar proteins [19, 20]. Given the diversity of anti-phage defenses systems, a matching diversity of yet unknown anti-cellular defenses functions is probably buried into the phage genomic “dark-matter” awaiting discovery.…”

Section: Introductionmentioning

confidence: 99%

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Genetic mining of newly isolated Salmophages for phage therapy

Gendre

Ansaldi

Olivenza

et al. 2022

Preprint

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Salmonella enterica – a Gram negative zoonotic bacterium – is mainly a food-borne pathogen and the main cause of diarrhea in humans worldwide. Main reservoirs are found in poultry farms but also in wild birds. The development of antibiotic resistance in S. enterica species raises concerns about the future of efficient therapies against this pathogen and revives the interest in bacteriophages as a useful therapy against bacterial infections. Here we aimed at deciphering and functionally annotate 10 new Salmonella phage genomes isolated in Spain in the light of phage therapy. We designed a bioinformatic pipeline using available building blocks to de novo assemble genomes and perform syntaxic annotation. We then used genome-wide analyses for taxonomic annotation enabled by vContact2 and VICTOR. We were also particularly interested in improving functional annotation using remote homologies detection and comparisons with the recently published phage-specific PHROG protein database. We finally searched for useful functions for phage therapy such as systems encoded by the phage to circumvent cellular defenses with a particular focus on anti-CRIPSR proteins. We thus were able to genetically characterized nine virulent phages and one temperate phage and identified putative functions relevant to the formulation of phage cocktails for Salmonella biocontrol.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic mining of newly isolated Salmophages for phage therapy

Gendre

Ansaldi

Olivenza

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Undoubtedly, co-evolution works both ways, and phages, therefore, evolved their own arsenal to counter cellular defenses. One can cite anti-RM or anti-CRISPR proteins [ 18 ] as well as the newly discovered anti-CBASS and anti-Pycsar proteins [ 19 , 20 ]. Given the diversity of anti-phage defense systems, a matching diversity of yet unknown anti-cellular defense functions is probably buried in the phage genomic “dark-matter” awaiting discovery.…”

Section: Introductionmentioning

confidence: 99%

Genetic Mining of Newly Isolated Salmophages for Phage Therapy

Gendre

Ansaldi

Olivenza

et al. 2022

IJMS

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Salmonella enterica, a Gram-negative zoonotic bacterium, is mainly a food-borne pathogen and the main cause of diarrhea in humans worldwide. The main reservoirs are found in poultry farms, but they are also found in wild birds. The development of antibiotic resistance in S. enterica species raises concerns about the future of efficient therapies against this pathogen and revives the interest in bacteriophages as a useful therapy against bacterial infections. Here, we aimed to decipher and functionally annotate 10 new Salmonella phage genomes isolated in Spain in the light of phage therapy. We designed a bioinformatic pipeline using available building blocks to de novo assemble genomes and perform syntaxic annotation. We then used genome-wide analyses for taxonomic annotation enabled by vContact2 and VICTOR. We were also particularly interested in improving functional annotation using remote homologies detection and comparisons with the recently published phage-specific PHROG protein database. Finally, we searched for useful functions for phage therapy, such as systems encoded by the phage to circumvent cellular defenses with a particular focus on anti-CRISPR proteins. We, thus, were able to genetically characterize nine virulent phages and one temperate phage and identify putative functions relevant to the formulation of phage cocktails for Salmonella biocontrol.

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“…Related cyclic-oligonucleotide synthase and effector pairs have been subsequently discovered and some were shown to have phage defense functions [17]. Collectively, these anti-phage systems are known as cyclic oligonucleotide-based antiphage signaling systems (CBASS) [18]. Moreover, it is now apparent that the first gene of the VSP-I island, vc0175, encodes a functional deoxycytidine deaminase named AvcD [19, 20].…”

Section: Introductionmentioning

confidence: 99%

The Vibrio cholerae Seventh Pandemic islands act in tandem to defend against a circulating phage

O’Hara

Alam

2022

Preprint

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The current circulating pandemic El Tor biotype of Vibrio cholerae has persisted for over sixty years and is characterized by its acquisition of two unique genomic islands called the Vibrio Seventh Pandemic Islands 1 and 2 (VSP-I and VSP-II). However, the functions of most of the genes on VSP-I and VSP-II are unknown and the advantages realized by El Tor through these two islands are not clear. Recent studies have broadly implicated these two mobile genetic elements with phage defense. Still, protection against phage infection through these islands has not been observed directly in any V. cholerae El Tor biotype. Here we report the isolation of a circulating phage from a cholera patient stool sample and demonstrate that propagation of this phage in its native host is inhibited by elements in both VSP-I and VSP-II, providing direct evidence for the role of these genomic islands in phage defense. Moreover, we show that these defense systems are regulated by quorum sensing and active only at certain cell density. Finally, we have isolated a naturally occurring phage variant that is resistant to the defense conferred by the VSP islands, illustrating the countermeasures used by phages to evade these defense mechanisms. Together, this work demonstrates a functional role for the VSPs in V. cholerae and highlights the key regulatory and mechanistic insights that can be gained by studying anti-phage systems in their native contexts.SIGNIFICANCE (AUTHOR SUMMARY)The current pandemic strain of Vibrio cholerae carries two unique genomic islands. How these two islands confer evolutionary advantage to the pathogen is unknown. We show here the identification of a circulating phage that is sensitive to the defense systems present on these two islands and demonstrate how phage variants can evade these defenses. Our studies provide the first direct evidence showing the importance of these genomic islands in defending against phage in their native environments; and in doing so provide novel insight into the mechanisms of these highly conserved defense elements.

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Bacteriophages antagonize cGAS-like immunity in bacteria

Cited by 17 publications

References 33 publications

Genetic mining of newly isolated Salmophages for phage therapy

Genetic mining of newly isolated Salmophages for phage therapy

Genetic Mining of Newly Isolated Salmophages for Phage Therapy

The Vibrio cholerae Seventh Pandemic islands act in tandem to defend against a circulating phage

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