Pseudomonas aeruginosaVirulence Analyzed in aDictyostelium discoideumHost System

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Abstract
Pseudomonas aeruginosais an important opportunistic pathogen that produces a variety of cell-associated and secreted virulence factors.P. aeruginosainfections are difficult to treat effectively because of the rapid emergence of antibiotic-resistant strains. In this study, we analyzed whether the amoebaDictyostelium discoideumcan be used as a simple model system to analyze the virulence ofP. aeruginosastrains. The virulent wild-type strain PAO1 was shown to inhibit growth ofD. discoideum. Isogenic mutants deficient in thelasquorum-sensing system were almost as inhibitory as the wild type, whilerhlquorum-sensing mutants permitted growth ofDictyosteliumcells. Therefore, in this model system, factors controlled by therhlquorum-sensing system were found to play a central role. Among these, rhamnolipids secreted by the wild-type strain PAO1 could induce fast lysis ofD. discoideumcells. By using this simple model system, we predicted that certain antibiotic-resistant mutants ofP. aeruginosashould show reduced virulence. This result was confirmed in a rat model of acute pneumonia. Thus,D. discoideumcould be used as a simple nonmammalian host system to assess pathogenicity ofP. aeruginosa.