Engineered Phage Modulates Quorum Sensing and Biofilm Formation in Pseudomonas aeruginosa

Domenico Franco1, Salvatore Papasergi2, Francesco Mediati1,3

  • 1Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.

Microorganisms
|May 27, 2026
PubMed

Insights

An engineered phage particle, P9b, selectively targets Pseudomonas aeruginosa virulence without killing bacteria. It disrupts quorum sensing (QS) and reduces biofilm formation, offering a novel antivirulence strategy.

Area of Science:

  • Microbiology
  • Bacteriology
  • Molecular Biology

Background:

  • * Pseudomonas aeruginosa is a Gram-negative pathogen causing persistent infections.
  • * Quorum sensing (QS) regulates virulence in P. aeruginosa, particularly in biofilms.
  • * Current treatments face challenges due to resistance and biofilm persistence.

Purpose of the Study:

  • * To investigate the antivirulence activity of an engineered M13-derived phage-display particle (P9b).
  • * To assess P9b's effect on P. aeruginosa quorum sensing and biofilm formation.
  • * To evaluate P9b's potential as a non-lytic antivirulence therapeutic.

Main Methods:

  • * Selection of P9b for specific binding to P. aeruginosa.
  • * Assessment of P9b's impact on bacterial growth and biofilm metabolic activity.
  • * Transcriptional analysis of QS regulators and virulence genes.
  • * Testing P9b activity against clinical isolates.

Main Results:

  • * P9b induced a transient delay in planktonic growth but did not affect long-term proliferation.
  • * P9b significantly reduced biofilm metabolic activity and pyocyanin production.
  • * Downregulation of QS regulators (lasI, lasR, rhlI, rhlR) and modulation of phenazine genes observed.
  • * P9b demonstrated efficacy against diverse clinical isolates.

Conclusions:

  • * P9b acts as a selective, non-lytic modulator of P. aeruginosa virulence.
  • * P9b effectively attenuates QS-regulated phenotypes and biofilm formation.
  • * Engineered phages represent a promising platform for antivirulence strategies against persistent infections.

Related Concept Videos

Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
Bacterial Signaling01:30

Bacterial Signaling

Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
Biofilms01:29

Biofilms

Biofilms are complex communities of microorganisms encased in a self-produced extracellular polysaccharide matrix attached to surfaces. These microbial consortia can include single or multiple species, providing enhanced survival benefits by forming organized, multilayered structures.The formation of biofilms occurs through four key stages: attachment, colonization, development, and dispersal.During attachment, free-swimming planktonic cells adhere to a surface, often facilitated by...