Journal article
Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system
Proceedings of the National Academy of Sciences - PNAS, v 103(5), pp 1528-1533
31 Jan 2006
PMID: 16432199
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system
- Creators
- Stefan Pukatzki - Center for Human GeneticsAmy T. MaDerek Sturtevant - Center for Human GeneticsBryan Krastins - Center for Human GeneticsDavid Sarracino - Center for Human GeneticsWilliam C. NelsonJohn F. Heidelberg - Center for Human GeneticsJohn J. Mekalanos - Center for Human Genetics
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 103(5), pp 1528-1533
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000235094300067
- Scopus ID
- 2-s2.0-31944433740
- Other Identifier
- 991020830155504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology