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

Caleb M. Schwartzkopf, Véronique L. Taylor, Marie Christine Groleau, Dominick R. Faith, Amelia K. Schmidt, Tyrza L. Lamma, Diane M. Brooks, Eric Déziel, Karen L. Maxwell, Patrick R. Secor

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)116-128
Number of pages13
JournalMolecular Microbiology
Volume121
Issue number1
DOIs
StatePublished - Jan 2024

Keywords

  • PQS quorum sensing
  • Pseudomonas aeruginosa
  • filamentous Pf bacteriophage
  • phage-bacteria interactions
  • pyocyanin virulence factor
  • quorum sensing inhibitor
  • Signal Transduction
  • Pseudomonas aeruginosa/genetics
  • Bacteriophages/metabolism
  • Quorum Sensing/genetics
  • Quinolones
  • Bacterial Proteins/metabolism
  • Virus Replication

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