Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility

TL;DR

This review synthesizes current understanding of *Pseudomonas aeruginosa* as a versatile opportunistic pathogen, covering its ecology, quorum sensing, biofilm biology, virulence, evolution and antimicrobial resistance. It argues that the bacterium's genomic variability, metabolic flexibility and phenotypic heterogeneity underpin its success in both environmental and clinical settings, and highlights emerging therapeutic strategies.

Key findings

• *P. aeruginosa* is generally rare in pristine environments but enriched in human-impacted habitats: it was found in only 12% of uncontaminated environmental samples, with higher distribution in animal faeces and compost (32%) versus soil and rhizosphere (7%) or environmental water (0%).
• The canonical hierarchical quorum sensing network (las → rhl/PQS) is not universal; many clinical and environmental isolates carry inactivating LasR mutations and have rewired the circuitry to LasR-independent activation of rhl, prompting interest in RhlR as a therapeutic target.
• In human infections, bacteria often grow as biofilm aggregates rather than surface-attached biofilms, with more than 50% of bacterial biomass in aggregates smaller than 100 μm³ in both acute and chronic lung infections.
• Tn-seq studies identify cofactor biosynthesis (purines, riboflavin, pantothenate, pyridoxal phosphate, polyamines, diaminopimelate, chorismate) rather than carbon catabolism as critical for fitness in cystic fibrosis sputum; long-chain fatty acid oxidation (faoAB) is critical in murine wound models; and a three-gene operon (srgABC) enhances serum resistance, with srgA overexpression increasing plasma survival up to 100-fold.
• Resistance in mixed-strain populations evolves rapidly mainly through natural selection of pre-existing resistant strains rather than de novo mutation or horizontal gene transfer, with trade-offs between resistance and growth rate.

Methods

• Narrative review article synthesizing published literature on *P. aeruginosa* ecology, evolution, pathogenesis and antimicrobial susceptibility; no primary experimental data are reported.
• Draws on cited studies including environmental sampling and meta-analysis across three countries/continents, experimental evolution work, Tn-seq screens in murine wound models, human plasma and cystic fibrosis sputum, and clinical epidemiology of sequence types.
• Covers quorum sensing (las, rhl, PQS systems), biofilm matrix components (alginate, Psl, Pel, eDNA, c-di-GMP), virulence factors (T3SS effectors, exotoxin A, proteases, rhamnolipids, phenazines, HCN), nutritional immunity and iron acquisition, and treatment strategies.

Limitations

• The paper states that the mechanisms producing biofilm aggregation in vivo remain unclear, that the clinical relevance of in vitro biofilm studies is uncertain, and that future in vivo work will require preclinical models accurately replicating human infection biology.
• The paper notes that social cheating by lasR mutants has been supported in vitro and in murine models but "has never been demonstrated in human infection," and that the emergence of LasR mutants in chronic infections remains poorly understood.
• Evident from the text: as a review, it synthesizes existing findings rather than presenting new data, and several cited conclusions (for example, aggregation mechanisms, heteroresistance prevalence) rest on evidence the authors themselves describe as incomplete or of unclear in vivo relevance.