If you need an accessible version of this item please contact JSTOR User Support

Identification of a Conserved Bacterial Protein Secretion System in Vibrio cholerae Using the Dictyostelium Host Model System

Stefan Pukatzki, Amy T. Ma, Derek Sturtevant, Bryan Krastins, David Sarracino, William C. Nelson, John F. Heidelberg and John J. Mekalanos
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 5 (Jan. 31, 2006), pp. 1528-1533
Stable URL: http://www.jstor.org/stable/30048406
Page Count: 6
  • Download PDF
  • Cite this Item

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If you need an accessible version of this item please contact JSTOR User Support
Identification of a Conserved Bacterial Protein Secretion System in Vibrio cholerae Using the Dictyostelium Host Model System
Preview not available

Abstract

The bacterium Vibrio cholerae, like other human pathogens that reside in environmental reservoirs, survives predation by unicellular eukaryotes. Strains of the O1 and O139 serogroups cause cholera, whereas non-O1/non-O139 strains cause human infections through poorly defined mechanisms. Using Dictyostelium discoideum as a model host, we have identified a virulence mechanism in a non-O1/non-O139 V. cholerae strain that involves extracellular translocation of proteins that lack N-terminal hydrophobic leader sequences. Accordingly, we have named these genes "VAS" genes for virulence-associated secretion, and we propose that these genes encode a prototypic "type VI" secretion system. We show that vas genes are required for cytotoxicity of V. cholerae cells toward Dictyostelium amoebae and mammalian J774 macrophages by a contact-dependent mechanism. A large number of Gram-negative bacterial pathogens carry genes homologous to vas genes and potential effector proteins secreted by this pathway (i.e., hemolysin-coregulated protein and VgrG). Mutations in vas homologs in other bacterial species have been reported to attenuate virulence in animals and cultured macrophages. Thus, the genes encoding the VAS-related, type VI secretion system likely play an important conserved function in microbial pathogenesis and represent an additional class of targets for vaccine and antimicrobial drug-based therapies.

Page Thumbnails

  • Thumbnail: Page 
1528
    1528
  • Thumbnail: Page 
1529
    1529
  • Thumbnail: Page 
1530
    1530
  • Thumbnail: Page 
1531
    1531
  • Thumbnail: Page 
1532
    1532
  • Thumbnail: Page 
1533
    1533