Profiling Early Infection Responses: Pseudomonas Aeruginosa Eludes Host Defenses by Suppressing Antimicrobial Peptide Gene Expression

Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2573-8. doi: 10.1073/pnas.0409588102. Epub 2005 Feb 4.

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 model Drosophila melanogaster to dissect and identify early host responses that function in the initiation and progression of Pseudomonas aeruginosa pathogenesis. First, we use immune potentiation and genetic studies to demonstrate that flies mount a heightened defense against the highly virulent P. aeruginosa strain 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 the Drosophila early 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 by P. aeruginosa in the initial stages of its host interaction: suppression of Drosophila defense 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 of P. aeruginosa-human infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / genetics*
  • Drosophila Proteins / genetics
  • Drosophila melanogaster
  • Gene Expression Profiling
  • Humans
  • Immunity, Innate / genetics
  • Pseudomonas Infections / etiology*
  • Pseudomonas Infections / genetics
  • Pseudomonas Infections / immunology
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / pathogenicity*
  • Receptors, Cell Surface / genetics
  • Signal Transduction
  • Suppression, Genetic
  • Toll-Like Receptors
  • Virulence

Substances

  • Antimicrobial Cationic Peptides
  • Drosophila Proteins
  • Receptors, Cell Surface
  • Tl protein, Drosophila
  • Toll-Like Receptors
  • imd protein, Drosophila