The human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum
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Updated: Aug 10, 2026

Tractable Mammalian Cell Infections with Protozoan-primed Bacteria
Published on: April 2, 2013
Stefan Pukatzki1, Richard H Kessin, John J Mekalanos
1Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. stefan_pukatzki@hms.harvard.edu
Abstract:
Genetically accessible host models are useful for studying microbial pathogenesis because they offer the means to identify novel strategies that pathogens use to evade immune mechanisms, cause cellular injury, and induce disease. We have developed conditions under which the human pathogen Pseudomonas aeruginosa infects Dictyostelium discoideum, a genetically tractable eukaryotic organism. When D. discoideum is plated on nutrient agar plates with different P. aeruginosa strains, the bacteria form lawns on these plates with amoebae embedded in them. Virulent P. aeruginosa strains kill these amoebae and leave an intact bacterial lawn. A number of P. aeruginosa mutants have been identified that are avirulent in this assay. Amoebae feed on these bacteria and form plaques in their bacterial lawns. One avirulent mutant strain carries an insertional mutation in the lasR gene. LasR is a transcription factor that controls a number of virulence genes in a density-dependent fashion. Another class of avirulent P. aeruginosa mutants is defective in type III secretion. One mutant lacks the PscJ protein, a structural component of the secretion apparatus, suggesting that cytotoxins are injected into the D. discoideum cell. One of these cytotoxins is ExoU, and exoU mutants are avirulent toward D. discoideum. Complementation of the lasR and exoU mutations restores virulence. Therefore, P. aeruginosa uses conserved virulence pathways to kill D. discoideum.
Insights
Pseudomonas aeruginosa uses conserved virulence pathways to infect and kill Dictyostelium discoideum. This study identifies key bacterial genes, like lasR and exoU, essential for pathogenesis in this model system.
Area of Science:
- Microbial Pathogenesis
- Host-Pathogen Interactions
- Model Organisms in Biology
Background:
- Genetically accessible host models are crucial for understanding microbial pathogenesis.
- Identifying pathogen evasion and disease induction mechanisms requires suitable models.
Purpose of the Study:
- To establish and utilize a model system for studying the human pathogen Pseudomonas aeruginosa.
- To investigate the virulence factors and pathways employed by P. aeruginosa in host infection.
Main Methods:
- Infection of the genetically tractable eukaryote Dictyostelium discoideum by P. aeruginosa.
- Identification of avirulent P. aeruginosa mutants through plaque assays.
- Genetic analysis of virulence factors including lasR and type III secretion system components (PscJ, ExoU).
Main Results:
- P. aeruginosa successfully infects and kills D. discoideum, forming intact bacterial lawns.
- Mutants in lasR and type III secretion (PscJ, ExoU) are avirulent, forming plaques.
- Complementation of lasR and exoU mutations restores virulence, confirming their roles.
Conclusions:
- P. aeruginosa utilizes conserved virulence pathways, including quorum sensing (LasR) and type III secretion (ExoU), to cause disease in D. discoideum.
- This model system effectively identifies essential virulence factors of P. aeruginosa.
- The findings highlight conserved mechanisms of bacterial pathogenesis.
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