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| Subject Categories: Microbiology & Pathogens |
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| The EMBO Journal
(2003) 22, 1451–1460, doi:10.1093/emboj/cdg159 |
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| Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening |
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| C.Léopold Kurz1, Sophie Chauvet2, Emmanuel Andrès3, Marianne Aurouze4, Isabelle Vallet4, Gérard P.F. Michel4, Mitch Uh5, Jean Celli5, 6, Alain Filloux4, Sophie de Bentzmann4, Ivo Steinmetz7, Jules A. Hoffmann3, B.Brett Finlay5, Jean-Pierre Gorvel1, Dominique Ferrandon3 and Jonathan J. Ewbank1 |
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1 Centre d'Immunologie de Marseille Luminy, INSERM/CNRS/Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France 2 Present address: INSERM U382, IBDM, Campus de Luminy, Case 907, 13288 Marseille cedex 9, France 3 Institut de Biologie Moléculaire et Cellulaire, UPR 9022 du CNRS, 15 rue R.Descartes, 67084 Strasbourg cedex, France 4 LISM/IBSM, 31 Ch.J.Aiguier, 13402 Marseille cedex 20, France 5 Biotechnology Laboratory, University of British Columbia, 237-6174 University Boulevard, Vancouver, BC, V6T 1Z3 Canada 6 Present address: Centre d'Immunologie de Marseille Luminy, 13288 Marseille cedex 9, France 7 Institute of Medical Microbiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany To whom correspondence should be addressed Jonathan J. Ewbank, ewbank@ciml.univ-mrs.fr Received 9 December 2002; Revised 13 February 2003; Accepted 17 February 2003. |
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| Abstract |
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| 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 produc tion. 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. |
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| Keywords: Caenorhabditis elegans, cytotoxicity, insertional mutagenesis, iron transport, LPS |
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