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Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system
Pierre Cosson1, Laurence Zulianello, Olivier Join-Lambert
1Département de Morphologie, Université de Genève, Centre Médical Universitaire, CH-1211 Geneva 4, Switzerland.
Abstract:
Pseudomonas aeruginosa is an important opportunistic pathogen that produces a variety of cell-associated and secreted virulence factors. P. aeruginosa infections are difficult to treat effectively because of the rapid emergence of antibiotic-resistant strains. In this study, we analyzed whether the amoeba Dictyostelium discoideum can be used as a simple model system to analyze the virulence of P. aeruginosa strains. The virulent wild-type strain PAO1 was shown to inhibit growth of D. discoideum. Isogenic mutants deficient in the las quorum-sensing system were almost as inhibitory as the wild type, while rhl quorum-sensing mutants permitted growth of Dictyostelium cells. Therefore, in this model system, factors controlled by the rhl quorum-sensing system were found to play a central role. Among these, rhamnolipids secreted by the wild-type strain PAO1 could induce fast lysis of D. discoideum cells. By using this simple model system, we predicted that certain antibiotic-resistant mutants of P. aeruginosa should show reduced virulence. This result was confirmed in a rat model of acute pneumonia. Thus, D. discoideum could be used as a simple nonmammalian host system to assess pathogenicity of P. aeruginosa.
Insights
Dictyostelium discoideum, a simple amoeba, effectively models Pseudomonas aeruginosa virulence. Rhamnolipids controlled by the rhl quorum-sensing system are key virulence factors, and this model predicts antibiotic resistance reduces P. aeruginosa pathogenicity.
Area of Science:
- Microbiology
- Pathogen Research
- Model Organism Studies
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen causing difficult-to-treat infections due to rising antibiotic resistance.
- Virulence factors, both cell-associated and secreted, contribute to P. aeruginosa pathogenicity.
- Developing efficient models to study virulence is crucial for understanding and combating P. aeruginosa infections.
Purpose of the Study:
- To evaluate Dictyostelium discoideum as a simple, non-mammalian model system for analyzing P. aeruginosa virulence.
- To investigate the role of quorum-sensing systems (las and rhl) in P. aeruginosa pathogenicity using D. discoideum.
- To determine if D. discoideum can predict virulence changes in P. aeruginosa, particularly in antibiotic-resistant strains.
Main Methods:
- Utilizing the virulent wild-type P. aeruginosa strain PAO1 and its isogenic mutants (las and rhl quorum-sensing deficient).
- Assessing the inhibitory effect of P. aeruginosa strains on the growth of Dictyostelium discoideum.
- Analyzing the role of secreted rhamnolipids in D. discoideum lysis.
- Correlating findings from the D. discoideum model with a rat model of acute pneumonia for antibiotic-resistant strains.
Main Results:
- The virulent P. aeruginosa strain PAO1 inhibited D. discoideum growth.
- Mutants deficient in the las quorum-sensing system showed similar inhibition to the wild type.
- Mutants deficient in the rhl quorum-sensing system allowed D. discoideum growth, indicating the rhl system's central role.
- Secreted rhamnolipids were identified as potent inducers of D. discoideum lysis.
- The D. discoideum model accurately predicted reduced virulence in antibiotic-resistant P. aeruginosa strains, confirmed in a rat pneumonia model.
Conclusions:
- Dictyostelium discoideum serves as a valuable and simple non-mammalian model for assessing P. aeruginosa pathogenicity.
- The rhl quorum-sensing system and its secreted factors, such as rhamnolipids, are critical for P. aeruginosa virulence.
- This model system can effectively predict virulence changes associated with antibiotic resistance in P. aeruginosa infections.