Tripartite interactions between filamentous Pf4 bacteriophage, Pseudomonas aeruginosa, and bacterivorous nematodes

Schwartzkopf, Caleb M; Robinson, Autumn J; Ellenbecker, Mary; Faith, Dominick R; Schmidt, Amelia K; Brooks, Diane M.; Lewerke, Lincoln; Voronina, Ekaterina; Dandekar, Ajai A.; Secor, Patrick R.

doi:10.1371/journal.ppat.1010925

Cited by 5 publications

(18 citation statements)

References 70 publications

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“…In recent work, we made similar observations in a Caenorhabditis elegans nematode infection model—bacteria lacking the Pf4 prophage are less virulent compared to isogenic Pf lysogens (Schwartzkopf et al., 2023). In this system, Pf4 modulates P. aeruginosa virulence potential by downregulating PQS signaling and reducing the production of the quorum‐regulated virulence factor pyocyanin (Schwartzkopf et al., 2023). However, how Pf4 suppresses PQS signaling and how PQS signaling may affect Pf4 replication is not known.…”

Section: Introductionsupporting

confidence: 67%

“…Deleting the Pf4 prophage from the P. aeruginosa PAO1 chromosome reduces bacterial virulence potential in mouse lung (Rice et al., 2009) and wound (Sweere et al., 2019) infection models. In recent work, we made similar observations in a Caenorhabditis elegans nematode infection model—bacteria lacking the Pf4 prophage are less virulent compared to isogenic Pf lysogens (Schwartzkopf et al., 2023). In this system, Pf4 modulates P. aeruginosa virulence potential by downregulating PQS signaling and reducing the production of the quorum‐regulated virulence factor pyocyanin (Schwartzkopf et al., 2023).…”

Section: Introductionsupporting

confidence: 67%

“…PfsE inhibition of PqsA increases Pf4 replication efficiency, consistent with a role for PQS signaling in regulating bacterial behaviors related to phage defense. Notably, PfsE has been previously characterized as an inner membrane protein that binds to the type IV pili protein PilC, which inhibits type IV pili extension and protects P. aeruginosa from superinfection by additional Pf4 virions or from infection by other type IV pili‐dependent phages (Schwartzkopf et al., 2023). We believe the simultaneous inhibition of PQS signaling and type IV pili by PfsE acts to suppress host defenses while at the same time protecting the susceptible host from competing phages.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionsupporting

confidence: 67%

Section: Introductionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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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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“…Pf4 is known to suppress PQS and Rhl quorum sensing in P. aeruginosa PAO1 (12, 13, 22). We hypothesized that Pf phages would likewise modulate quorum sensing in the Pf deletion strains we constructed here.…”

Section: Resultsmentioning

confidence: 99%

“…Pyocyanin is a redox-active quorum-regulated virulence factor (26). Deleting the Pf4 prophage from PAO1 enhances pyocyanin production (27). We observed increased pyocyanin production in all ΔPf strains tested except CPA0053, which did not produce much pyocyanin under any condition tested ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Targeted deletion of Pf prophages from diversePseudomonas aeruginosaisolates impacts quorum sensing and virulence traits

Schmidt,

Schwartzkopf,

Pourtois

et al. 2023

Preprint

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Pseudomonas aeruginosais an opportunistic bacterial pathogen that commonly causes medical hardware, wound, and respiratory infections. Temperate filamentous Pf phages that infectP. aeruginosaimpact numerous bacterial virulence phenotypes. Most work on Pf phages has focused on strain Pf4 and its hostP. aeruginosaPAO1. Expanding from Pf4 and PAO1, this study explores diverse Pf strains infectingP. aeruginosaclinical isolates. We describe a simple technique targeting the Pf lysogeny maintenance gene,pflM(PA0718), that enables the effective elimination of Pf prophages from diverseP. aeruginosahosts. This study also assesses the effects different Pf phages have on host quorum sensing, biofilm formation, virulence factor production, and virulence. Collectively, this research not only introduces a valuable tool for Pf prophage elimination from diverseP. aeruginosaisolates, but also advances our understanding of the complex relationship betweenP. aeruginosaand filamentous Pf phages.ImportancePseudomonas aeruginosais an opportunistic bacterial pathogen that is frequently infected by filamentous Pf phages (viruses) that integrate into its chromosome, affecting behavior. While prior work has focused on Pf4 and PAO1, this study investigates diverse Pf strains in clinical isolates. A simple method targeting the deletion of the Pf lysogeny maintenance genepflM(PA0718) effectively eliminates Pf prophages from clinical isolates. The research evaluates the impact Pf prophages have on bacterial quorum sensing, biofilm formation, and virulence phenotypes. This work introduces a valuable tool to eliminate Pf prophages from clinical isolates and advances our understanding ofP. aeruginosaand filamentous Pf phage interactions.

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Control of lysogeny and antiphage defense by a prophage-encoded kinase-phosphatase module

Guo,

Tang,

Sit

et al. 2024

Nat Commun

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The filamentous ‘Pf’ bacteriophages of Pseudomonas aeruginosa play roles in biofilm formation and virulence, but mechanisms governing Pf prophage activation in biofilms are unclear. Here, we identify a prophage regulatory module, KKP (kinase-kinase-phosphatase), that controls virion production of co-resident Pf prophages and mediates host defense against diverse lytic phages. KKP consists of Ser/Thr kinases PfkA and PfkB, and phosphatase PfpC. The kinases have multiple host targets, one of which is MvaU, a host nucleoid-binding protein and known prophage-silencing factor. Characterization of KKP deletion and overexpression strains with transcriptional, protein-level and prophage-based approaches indicates that shifts in the balance between kinase and phosphatase activities regulate phage production by controlling MvaU phosphorylation. In addition, KKP acts as a tripartite toxin-antitoxin system that provides defense against some lytic phages. A conserved lytic phage replication protein inhibits the KKP phosphatase PfpC, stimulating toxic kinase activity and blocking lytic phage production. Thus, KKP represents a phosphorylation-based mechanism for prophage regulation and antiphage defense. The conservation of KKP gene clusters in >1000 diverse temperate prophages suggests that integrated control of temperate and lytic phage infection by KKP-like regulatory modules may play a widespread role in shaping host cell physiology.

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Tripartite interactions between filamentous Pf4 bacteriophage, Pseudomonas aeruginosa, and bacterivorous nematodes

Cited by 5 publications

References 70 publications

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

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

Targeted deletion of Pf prophages from diversePseudomonas aeruginosaisolates impacts quorum sensing and virulence traits

Control of lysogeny and antiphage defense by a prophage-encoded kinase-phosphatase module

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