title: Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model.
abstract: An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.
authors: Equipe Fondation Recherche Médicale, Unité Propre de Recherche 9022 du Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, F67084 Strasbourg Cedex, France.
authors: Stefanie
authors: S
authors: Limmer
authors: Samantha
authors: S
authors: Haller
authors: Eliana
authors: E
authors: Drenkard
authors: Janice
authors: J
authors: Lee
authors: Shen
authors: S
authors: Yu
authors: Christine
authors: C
authors: Kocks
authors: Frederick M
authors: FM
authors: Ausubel
authors: Dominique
authors: D
authors: Ferrandon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D030801:Animals, Genetically Modified; D016470:Bacteremia / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D017344:Genes, Insect; D005814:Genes, Viral; D006458:Hemolymph / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D009154:Mutation; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D053038:Quorum Sensing / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; C086515:RhlR protein, Pseudomonas aeruginosa; D015534:Trans-Activators