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Published on: June 30, 2016
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.
Abstract:
Pseudomonas aeruginosa (P. aeruginosa) forms biofilms that are difficult to eliminate. The matrix protects the cells, efflux pumps reduce intracellular drug levels, and dormant subpopulations survive treatment. Routine minimum inhibitory concentration (MIC) testing does not account for these features, which helps explain why infections often continue even when therapy appears appropriate. This review describes how quorum-sensing (QS) and cyclic di-guanosine monophosphate (c-di-GMP) regulate matrix production, efflux activity, and dormancy within P. aeruginosa biofilms. Important matrix components, including Psl, Pel, alginate, and extracellular DNA, slow the movement of antimicrobial agents. Regulatory proteins such as sagS and brlR increase the activity of the MexAB-OprM and MexEF-OprN efflux systems, further reducing intracellular drug concentrations. Oxygen and nutrient limitation promote persister cells and viable but nonculturable cells, with both having the ability to survive antibiotic levels that would normally be lethal. These defenses explain the gap between MIC values and biofilm-specific measurements, such as the minimum biofilm inhibitory concentration and the minimum biofilm eradication concentration. This review also summarizes emerging antibiofilm strategies. These include QS inhibitors, compounds that lower c-di-GMP, such as nitric oxide donors, nanoparticles, depolymerases, bacteriophages, and therapies that are directed at host targets. Modern diagnostic tools, such as confocal laser scanning microscopy, optical coherence tomography, and Raman spectroscopy, improve detection and guide treatment planning. A staged therapeutic approach is presented that begins with the dispersal or loosening of the matrix, continues with targeted antibiotics, and concludes with support for immune clearance. Viewing these strategies within a One Health framework highlights the role of biofilms in clinical disease and in environmental reservoirs and supports more effective surveillance and prevention.
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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