Phenazine Metabolism and Biofilm Dynamics in Pseudomonas aeruginosa
Summary
Pseudomonas aeruginosa biofilms are underpinned by the synthesis and redox cycling of phenazine molecules, notably pyocyanin and phenazine-1-carboxylic acid, which act as extracellular electron shuttles. These metabolites modulate intracellular and extracellular electron flow, enabling cells in oxygen-limited microzones to maintain redox balance and sustain metabolic activity. Interactions between phenazines and matrix components, such as extracellular DNA, facilitate efficient electron transfer across biofilm layers, thereby shaping spatial heterogeneity in physiology. This metabolic stratification governs the distribution of nutrients and drugs, contributing to enhanced antibiotic tolerance. In clinical settings—such as chronic wounds and cystic fibrosis lung infections—phenazine-driven resilience of biofilms underlies treatment recalcitrance, highlighting the importance of targeting biosynthetic, redox and matrix-binding processes to disrupt community survival and improve therapeutic outcomes.
Research from Nature Portfolio
Recent studies have revealed that phenazine production within biofilms promotes metabolic heterogeneity and antibiotic tolerance. Using stable isotope labelling and chemical imaging, researchers visualised in situ how phenazine redox cycling sustains microaerobic metabolism in distinct strata of mature biofilms. This metabolic support is linked to the engagement of specific respiratory complexes and the differential utilisation of phenazines under varying carbon sources. Mutant strains lacking key respiratory enzymes exhibited diminished phenazine-dependent survival upon antibiotic challenge, highlighting targets for disrupting redox-mediated defence mechanisms.
Phenazine Metabolism and Biofilm Dynamics in Pseudomonas aeruginosa publication trend
The graph below shows the total number of articles in phenazine metabolism and biofilm dynamics in pseudomonas aeruginosa across all publications each year (not limited to Nature Index journals).
Technical terms
Phenazines: A class of redox-active secondary metabolites produced by P. aeruginosa that shuttle electrons between cells and external acceptors.
Redox cycling: Repeated reduction and oxidation of a molecule, allowing regeneration of its active form for ongoing electron transfer.
Extracellular electron transfer (EET): Movement of electrons from microbial cells through soluble or insoluble mediators to distant electron acceptors.
Biofilm matrix: A complex polymeric network of polysaccharides, proteins and extracellular DNA that embeds cells and retains metabolites.
Metabolic heterogeneity: Variation in metabolic states among cells within a biofilm, often driven by gradients of nutrients and electron acceptors.
References
- Cellular arrangement impacts metabolic activity and antibiotic tolerance in Pseudomonas aeruginosa biofilms.. PLOS Biology (2024).
- Pyocyanin-dependent electrochemical inhibition of Pseudomonas aeruginosa biofilms is synergistic with antibiotic treatment. mBio (2023).
- Extracellular DNA Promotes Efficient Extracellular Electron Transfer by Pyocyanin in Pseudomonas aeruginosa Biofilms. Cell (2020).
- Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms. Nature Communications (2019).
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