Abstract
Pseudomonas aeruginosa has long served as a model organism in microbiology, particularly for studies on gene expression, quorum sensing, antibiotic resistance, virulence and biofilm formation. Its genetic tractability has advanced the understanding of complex regulatory networks and experimental evolution. The versatility of this bacterium stems from its genomic variability, metabolic flexibility and phenotypic diversity, enabling it to thrive in diverse environments, both as a harmless saprophyte and an opportunistic human pathogen. P. aeruginosa can cause acute and chronic human infections, particularly in patients with underlying immune deficiencies. Its intrinsic antibiotic tolerance and resistance, together with its ability to produce multiple virulence factors while rapidly adapting to infection conditions, pose a major clinical challenge. In this Review, we explore key features contributing to the ecological and pathogenic versatility of P. aeruginosa. We examine the molecular mechanisms and ecological and evolutionary implications of quorum sensing and biofilm formation. We explore the virulence strategies and in vivo fitness determinants, as well as the evolutionary dynamics and global epidemiology of P. aeruginosa, with a focus on antimicrobial resistance. Finally, we discuss emerging strategies to control P. aeruginosa infections and address outstanding questions in the field.
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Acknowledgements
The authors thank the Cystic Fibrosis foundation for grants (WHITEL20A0 and WHITEL22G0) to M.W. and a postdoctoral fellowship to M.L. (LETIZI24G0-BASBAUM); the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) for funding to S.P.D. (R01AI153116 and R56AI184449) and M.W. (R01AI189786).
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M.W. is the co-founder and CSO of SynthBiome, Inc. M.L. and S.P.D. declare no competing interests.
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Glossary
- Bet hedging
-
Stochastic switching between phenotypic states to enhance population long-term fitness in fluctuating environmental conditions.
- Biogeography
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The spatial assembly and distribution of various organisms in an environment through time.
- Bridging aggregation
-
A mechanism of bacterial aggregation driven by electrostatic interactions between bacterial cell surfaces and polymers present in the environment.
- Depletion aggregation
-
A process in which the reduction of free energy through increased entropy of the whole system induces the stacked aggregation of bacterial cells in polymer-rich environments.
- Division of labour
-
Cooperating individuals specialize in carrying out specific tasks, providing an inclusive fitness benefit to all individuals involved.
- Self-sensing
-
Cell-autonomous and density-independent reception of signals produced by the same cell.
- Sociomicrobiology
-
Studies on the group behaviours of microorganisms.
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Letizia, M., Diggle, S.P. & Whiteley, M. Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility. Nat Rev Microbiol (2025). https://doi.org/10.1038/s41579-025-01193-8
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DOI: https://doi.org/10.1038/s41579-025-01193-8