Understanding Pseudomonas aeruginosa Biofilms: Quorum Sensing, c-di-GMP Signaling, and Emerging Antibiofilm

Ayman Elbehiry1, Eman Marzouk1, Husam M Edrees2

  • 1Department of Public Health, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia.

Microorganisms
|January 28, 2026
PubMed

Insights

Pseudomonas aeruginosa biofilms resist antibiotics through protective matrices, efflux pumps, and dormant cells. New strategies target quorum sensing, c-di-GMP, and use advanced diagnostics for effective treatment.

Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • Pseudomonas aeruginosa biofilms present significant challenges in treating chronic infections due to inherent resistance mechanisms.
  • Standard antimicrobial susceptibility testing (e.g., minimum inhibitory concentration) often fails to predict treatment outcomes in biofilm infections.
  • Biofilm formation involves complex regulation of matrix production, drug efflux, and cell dormancy.

Purpose of the Study:

  • To review the regulatory mechanisms of Pseudomonas aeruginosa biofilm formation and survival.
  • To discuss emerging antibiofilm strategies and diagnostic tools.
  • To propose a staged therapeutic approach for biofilm infections.

Main Methods:

  • Literature review of quorum sensing (QS) and cyclic di-guanosine monophosphate (c-di-GMP) roles in biofilm regulation.
  • Summary of antibiofilm agents including QS inhibitors, c-di-GMP modulators, nanoparticles, depolymerases, and bacteriophages.
  • Overview of advanced diagnostic techniques like confocal laser scanning microscopy and optical coherence tomography.

Main Results:

  • QS and c-di-GMP signaling pathways critically regulate biofilm matrix production, efflux pump activity, and cell dormancy.
  • Biofilm matrix components (Psl, Pel, alginate, eDNA) impede antimicrobial penetration.
  • Efflux systems (MexAB-OprM, MexEF-OprN) and physiological states (persister, VBNC cells) contribute to antibiotic tolerance.
  • Emerging strategies show promise in disrupting biofilm structure and eradicating embedded bacteria.
  • Advanced diagnostics aid in biofilm detection and treatment planning.

Conclusions:

  • Understanding biofilm regulatory networks is key to developing effective antibiofilm therapies.
  • A multi-pronged approach combining matrix dispersal, targeted antibiotics, and host immune support is recommended.
  • Integrating One Health principles is crucial for surveillance and prevention of P. aeruginosa biofilm infections in clinical and environmental settings.

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