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

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.

Targeted deletion of Pf prophages from diverse Pseudomonas aeruginosa isolates has differential impacts on quorum sensing and virulence traits

“…Deleting both Pf4 and Pf6 had no significant impact on Las or Rhl signaling, but PQS signaling was significantly upregulated in PAO1 ∆Pf4/Pf6 compared with the parental strain ( Fig. 4A ), which is consistent with prior work ( 12 , 24 ).…”

Enterococcal quorum-controlled protease alters phage infection

“…One way that phages are known to influence the bacterial response to infection is by modulating the cell density-dependent transcriptional program known as quorum sensing (24–27). Phage-mediated changes in quorum sensing gene regulation within a bacterial population can create an environment that is more permissible for infection (24, 25). For example, changes in quorum sensing can result in the modification of wall teichoic acids, a major phage receptor, which contributes to phage infectivity (28, 29).…”