title: Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening.
abstract: The human opportunistic pathogen Serratia marcescens is a bacterium with a broad host range, and represents a growing problem for public health. Serratia marcescens kills Caenorhabditis elegans after colonizing the nematode's intestine. We used C.elegans to screen a bank of transposon-induced S.marcescens mutants and isolated 23 clones with an attenuated virulence. Nine of the selected bacterial clones also showed a reduced virulence in an insect model of infection. Of these, three exhibited a reduced cytotoxicity in vitro, and among them one was also markedly attenuated in its virulence in a murine lung infection model. For 21 of the 23 mutants, the transposon insertion site was identified. This revealed that among the genes necessary for full in vivo virulence are those that function in lipopolysaccharide (LPS) biosynthesis, iron uptake and hemolysin production. Using this system we also identified novel conserved virulence factors required for Pseudomonas aeruginosa pathogenicity. This study extends the utility of C.elegans as an in vivo model for the study of bacterial virulence and advances the molecular understanding of S.marcescens pathogenicity.
authors.affiliation: Centre d'Immunologie de Marseille Luminy, INSERM/CNRS/Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France.
authors.forename: C Léopold
authors.initials: CL
authors.lastname: Kurz
authors.forename: Sophie
authors.initials: S
authors.lastname: Chauvet
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Andrès
authors.forename: Marianne
authors.initials: M
authors.lastname: Aurouze
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vallet
authors.forename: Gérard P F
authors.initials: GP
authors.lastname: Michel
authors.forename: Mitch
authors.initials: M
authors.lastname: Uh
authors.forename: Jean
authors.initials: J
authors.lastname: Celli
authors.forename: Alain
authors.initials: A
authors.lastname: Filloux
authors.forename: Sophie
authors.initials: S
authors.lastname: De Bentzmann
authors.forename: Ivo
authors.initials: I
authors.lastname: Steinmetz
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.forename: Dominique
authors.initials: D
authors.lastname: Ferrandon
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000382:microbiology*; D008969:Molecular Sequence Data; D009154:Mutation; D012706:Serratia marcescens / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence