AbstractBackgroundPseudomonas aeruginosais one of the most relevant human opportunistic bacterial pathogens. Two strains (PAO1 and PA14) have been mainly used as models for studying virulence ofP. aeruginosa. The strain PA14 is more virulent than PAO1 in a wide range of hosts including insects, nematodes and plants. Whereas some of the differences might be attributable to concerted action of determinants encoded in pathogenicity islands present in the genome of PA14, a global analysis of the differential host responses to theseP. aeruginosastrains has not been addressed. Little is known about the host response to infection withP. aeruginosaand whether or not the global host transcription is being affected as a defense mechanism or altered in the benefit of the pathogen. Since the social amoebaDictyostelium discoideumis a suitable host to study virulence ofP. aeruginosaand other pathogens, we used available genomic tools in this model system to study the transcriptional host response toP. aeruginosainfection.ResultsWe have compared the virulence of theP. aeruginosaPAO1 and PA14 usingD. discoideumand studied the transcriptional response of the amoeba upon infection. Our results showed that PA14 is more virulent inDictyosteliumthan PA01using different plating assays. For studying the differential response of the host to infection by these model strains,D. discoideumcells were exposed to eitherP. aeruginosaPAO1 orP. aeruginosaPA14 (mixed with an excess of the non-pathogenic bacteriumKlebsiella aerogenesas food supply) and after 4 hours, cellular RNA extracted. A three-way comparison was made using whole-genomeD. discoideummicroarrays between RNA samples from cells treated with the two different strains and control cells exposed only toK. aerogenes. The transcriptomic analyses have shown the existence of common and specific responses to infection. The expression of 364 genes changed in a similar way upon infection with one or another strain, whereas 169 genes were differentially regulated depending on whether the infecting strain was eitherP. aeruginosaPAO1 or PA14. Effects on metabolism, signalling, stress response and cell cycle can be inferred from the genes affected.ConclusionOur results show that pathogenicPseudomonasstrains invoke both a common transcriptional response fromDictyosteliumand a strain specific one, indicating that the infective process of bacterial pathogens can be strain-specific and is more complex than previously thought.