title: Specific host genes required for the killing of Klebsiella bacteria by phagocytes.
abstract: The amoeba Dictyostelium discoideum shares many traits with mammalian macrophages, in particular the ability to phagocytose and kill bacteria. In response, pathogenic bacteria use conserved mechanisms to fight amoebae and mammalian phagocytes. Here we developed an assay using Dictyostelium to monitor phagocyte-bacteria interactions. Genetic analysis revealed that the virulence of Klebsiella pneumoniae measured by this test is very similar to that observed in a mouse pneumonia model. Using this assay, two new host resistance genes (PHG1 and KIL1) were identified and shown to be involved in intracellular killing of K. pneumoniae by phagocytes. Phg1 is a member of the 9TM family of proteins, and Kil1 is a sulphotransferase. The loss of PHG1 resulted in Dictyostelium susceptibility to a small subset of bacterial species including K. pneumoniae. Remarkably, Drosophila mutants deficient for PHG1 also exhibited a specific susceptibility to K. pneumoniae infections. Systematic analysis of several additional Dictyostelium mutants created a two-dimensional virulence array, where the complex interactions between host and bacteria are visualized.
authors.affiliation: Athelas SA, Chemin des Aulx 18, 1228 Plan-les-Ouates, Geneva, Switzerland.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Benghezal
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Fauvarque
authors.forename: Régis
authors.initials: R
authors.lastname: Tournebize
authors.forename: Romain
authors.initials: R
authors.lastname: Froquet
authors.forename: Anna
authors.initials: A
authors.lastname: Marchetti
authors.forename: Evelyne
authors.initials: E
authors.lastname: Bergeret
authors.forename: Bernard
authors.initials: B
authors.lastname: Lardy
authors.forename: Gérard
authors.initials: G
authors.lastname: Klein
authors.forename: Philippe
authors.initials: P
authors.lastname: Sansonetti
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Charette
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004023:Dictyostelium / Q000254:growth & development / Q000382:microbiology / Q000502:physiology*; D004195:Disease Models, Animal; D004330:Drosophila / Q000254:growth & development / Q000382:microbiology / Q000502:physiology; D007711:Klebsiella pneumoniae / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000378:metabolism / Q000382:microbiology; D014774:Virulence
chemical_list: D008565:Membrane Proteins; C416668:Phg1 protein, Dictyostelium discoideum