Profiling early infection responses:Pseudomonas aeruginosaeludes host defenses by suppressing antimicrobial peptide gene expression

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Abstract
Insights into the host factors and mechanisms mediating the primary host responses after pathogen presentation remain limited, due in part to the complexity and genetic intractability of host systems. Here, we employ the modelDrosophila melanogasterto dissect and identify early host responses that function in the initiation and progression ofPseudomonas aeruginosapathogenesis. First, we use immune potentiation and genetic studies to demonstrate that flies mount a heightened defense against the highly virulentP. aeruginosastrain PA14 when first inoculated with strain CF5, which is avirulent in flies; this effect is mediated via the Imd and Toll signaling pathways. Second, we use whole-genome expression profiling to assess and compare theDrosophilaearly defense responses triggered by the PA14 vs. CF5 strains to identify genes whose expression patterns are different in susceptible vs. resistant host–pathogen interactions, respectively. Our results identify pathogenesis- and defense-specific genes and uncover a previously undescribed mechanism used byP. aeruginosain the initial stages of its host interaction: suppression ofDrosophiladefense responses by limiting antimicrobial peptide gene expression. These results provide insights into the genetic factors that mediate or restrict pathogenesis during the early stages of the bacterial–host interaction to advance our understanding ofP. aeruginosa-human infections.