Surrogate host succumbs to virulent Pseudomonas

Abstract

The complex interaction of bacterial pathogens with intractable host cells has led several investigators to explore genetically defined, easily exploited eukaryotic organisms as surrogate hosts. According to a recent report by Pukatzki et al. [1xThe human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum. Pukatzki, S et al. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 3159–3164Crossref | PubMed | Scopus (170)See all References[1], the free-living, single-celled amoeba Dictyostelium discoideum can now join plants, nematodes, fruit flies and mice as a model host organism for Pseudomonas aeruginosa.D. discoideum has previously been developed as a model for another Gram-negative pathogen, Legionella pneumophila [2xIntracellular growth of Legionella pneumophila in Dictyostelium discoideum, a system for genetic analysis of host–pathogen interactions. Solomon, J.M et al. Infect. Immun. 2000; 68: 2939–2947Crossref | PubMed | Scopus (146)See all References[2]. Unlike L. pneumophila, which infects and grows intracellularly within D. discoideum, P. aeruginosa is not primarily an intracellular pathogen. To identify genes associated with virulence, a simple plating assay was designed in which the amoebae are killed if they feed on virulent P. aeruginosa. Using this assay, two previously identified Pseudomonas virulence pathways were identified, a quorum-sensing transcription factor, LasR, and the type III secreted cytotoxin ExoU. These findings validated this system as a model for this host–pathogen interaction. In addition, these data provide a new starting point for a powerful genetic-based investigation of these virulence determinants. By contrast, elastase, pyocyanin and rhamnolipids, expression of which is controlled by LasR and which have been found to be associated with Pseudomonas virulence in other hosts, were discovered not to play a role in virulence in the amoebae. Thus, although simple-cell surrogate hosts can provide valuable genetic tools that can be used to reveal virulence pathways, it is not surprising that models using more complex hosts remain critical if we are to uncover the full repertoire of bacterial virulence factors.