Related Experiment Video
Updated: May 28, 2026

Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases
Published on: January 1, 2016
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.
Abstract:
Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen frequently associated with chronic and biofilm-related infections, largely driven by quorum sensing (QS)-related genes/phenotypes. In this study, we investigated the antivirulence activity of an engineered M13-derived phage-display particle (P9b), selected for specific binding to P. aeruginosa, which acts as a non-lytic modulator of QS through specific binding to a bacterial surface target. P9b induced a transient delay in early planktonic growth, without affecting long-term proliferation. In contrast, P9b significantly reduced biofilm-associated metabolic activity and pyocyanin production, consistent with an effect on QS-regulated pathways. Transcriptional analysis revealed significant downregulation of key QS regulators (lasI, lasR, rhlI, and rhlR) and modulation of phenazine biosynthesis genes (phzM downregulation and phzS upregulation), suggesting interference with QS-dependent regulatory circuits. Notably, P9b retained binding capacity and antibiofilm activity across clinically relevant P. aeruginosa isolates. Overall, these findings indicate that P9b acts as a selective, non-lytic modulator of virulence-associated traits, attenuating QS-regulated phenotypes without bactericidal effects. This study supports the potential of engineered filamentous phages as targeted antivirulence platforms for the development of innovative strategies against persistent and biofilm-associated infections.
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 Sensing
Bacterial Signaling
Regulation of Bacterial Virulence
Biofilms
