Pf4 Phage Variant Infection Reduces Virulence-Associated Traits in
            <i>Pseudomonas aeruginosa</i>

Tortuel, Damien; Tahrioui, Ali; David, Audrey; Cambronel, Mélyssa; Nilly, Flore; Clamens, Thomas; Maillot, Olivier; Barreau, Magalie; Feuilloley, Marc; Lesouhaitier, Olivier; Filloux, Alain; Bouffartigues, Emeline; Cornélis, Pierre; Chevalier, Sylvie

doi:10.1128/spectrum.01548-22

Cited by 19 publications

(20 citation statements)

References 128 publications

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“…Pertinent to our study, a recent report by Tortuel et al showed that P. aeruginosa infected with SI-Pf phage had reduced virulence in lettuce plant and Caenorhabditis elegans infection models (21). Tortuel et al reported decreased spread of the SI-Pf within the lettuce leaf, as well as a reduced rate of C. elegans mortality when compared to control, respectively.…”

Section: Introductionsupporting

confidence: 83%

“…Importantly, the specific mutations in the Pf chromosome that result in a super-infective phage were not well delineated. While some studies have detected mutations in the phage repressor and in the intergenic region between the repressor and the exsicionase gene, other have reported mutations in other phage genes such as PA0723, PA0724 and PA0725 (21). None of these had been experimentally validated as being at cause.…”

Section: Resultsmentioning

confidence: 99%

“…The rationale for our study were the prior observations by Tortuel et al . revealing P. aeruginosa infected with SI-Pf has reduced virulence in lettuce and C. elegans infection models (21). These models, have demonstrated value in identifying P. aeruginosa virulence factors and therefore hinted that SI-Pf treatment of infected wounds may ameliorate infection in mammals (36).…”

Section: Discussionmentioning

confidence: 99%

“…Pertinent to our study, a recent report by Tortuel et al . showed that P. aeruginosa infected with SI-Pf phage had reduced virulence in lettuce plant and Caenorhabditis elegans infection models (21). Tortuel et al .…”

Section: Introductionmentioning

confidence: 99%

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Engineered superinfective Pf phage prevents dissemination ofPseudomonas aeruginosain a mouse burn model

Prokopczuk

Campos-Gómez

et al. 2022

Preprint

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Pf is a filamentous bacteriophage integrated in the chromosome of most clinical isolates ofPseudomonas aeruginosa. Under stress conditions, mutations occurring in the Pf genome result in the emergence of super-infective variants of Pf (SI-Pf) that are capable of circumventing phage immunity; therefore SI-Pf can even infect Pf-lysogenizedP. aeruginosa. Herein, we identified specific mutations located between the repressor and the excisionase genes that result in the emergence of SI-Pf. Based on these findings, we genetically engineered a SI-Pf (eSI-Pf) and tested it as a phage therapy tool for the treatment of life-threateningP. aeruginosainfection of burns caused by strain PAO1. eSI-Pf was able to infect PAO1 biofilms formed in vitro on polystyrene and inhibited their formation when at high concentration. eSI-Pf also infected PAO1 present in burned skin wounds on mice but was not capable of maintaining a sustained reduction in bacterial burden beyond 24 hours. Importantly, and despite not lowering CFU/g of burn skin tissue, eSI-Pf treatment completely abolished the capability ofP. aeruginosato disseminate from the burn site to internal organs. Over the course of 10 days, this resulted in bacterial clearance and survival of all treated mice. We determined that eSI-Pf induced a small colony variant ofP. aeruginosathat was unable to disseminate systemically in our burned mouse model during acute infection. Our results suggest that eSI-Pf has potential as a phage therapy against highly recalcitrant antimicrobial resistantP. aeruginosainfections of burn wounds.

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Section: Introductionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Engineered superinfective Pf phage prevents dissemination ofPseudomonas aeruginosain a mouse burn model

Prokopczuk

Campos-Gómez

et al. 2022

Preprint

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“…F I G U R E 2 Pf4 replication downregulates P. aeruginosa quorum sensing and phenazine biosynthesis genes. RNAseq was performed on P. aeruginosa PAO1 infected with Pf4 compared to uninfected cultures in LB broth as described in reference (Tortuel et al, 2022). To confirm the results from the BATCH assay, we expressed Histagged PqsA and S-tagged PfsE in E. coli and purified His-tagged protein complexes by affinity chromatography (Figure 4e).…”

Section: The Pf4 Phage Protein Pfse Binds To Pqsamentioning

confidence: 99%

Inhibition of PQS signaling by the Pf bacteriophage protein PfsE enhances viral replication in Pseudomonas aeruginosa

Schwartzkopf,

Taylor,

Groleau

et al. 2023

Molecular Microbiology

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Quorum sensing, a bacterial signaling system that coordinates group behaviors as a function of cell density, plays an important role in regulating viral (phage) defense mechanisms in bacteria. The opportunistic pathogen Pseudomonas aeruginosa is a model system for the study of quorum sensing. P. aeruginosa is also frequently infected by Pf prophages that integrate into the host chromosome. Upon induction, Pf phages suppress host quorum sensing systems; however, the physiological relevance and mechanism of suppression are unknown. Here, we identify the Pf phage protein PfsE as an inhibitor of Pseudomonas Quinolone Signal (PQS) quorum sensing. PfsE binds to the host protein PqsA, which is essential for the biosynthesis of the PQS signaling molecule. Inhibition of PqsA increases the replication efficiency of Pf virions when infecting a new host and when the Pf prophage switches from lysogenic replication to active virion replication. In addition to inhibiting PQS signaling, our prior work demonstrates that PfsE also binds to PilC and inhibits type IV pili extension, protecting P. aeruginosa from infection by type IV pili‐dependent phages. Overall, this work suggests that the simultaneous inhibition of PQS signaling and type IV pili by PfsE may be a viral strategy to suppress host defenses to promote Pf replication while at the same time protecting the susceptible host from competing phages.

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Virulence-associated factors as targets for phage infection

de Melo,

Morency,

Moineau

2024

Current Opinion in Microbiology

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Pf4 Phage Variant Infection Reduces Virulence-Associated Traits in Pseudomonas aeruginosa

Cited by 19 publications

References 128 publications

Engineered superinfective Pf phage prevents dissemination ofPseudomonas aeruginosain a mouse burn model

Engineered superinfective Pf phage prevents dissemination ofPseudomonas aeruginosain a mouse burn model

Inhibition of PQS signaling by the Pf bacteriophage protein PfsE enhances viral replication in Pseudomonas aeruginosa

Virulence-associated factors as targets for phage infection

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