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Modulation of host cell function by the bacterial type IV secretion process: molecular basis of the translocation and the intracellular effector function of secreted virulence factors
Third-party funded project |
Project title |
Modulation of host cell function by the bacterial type IV secretion process: molecular basis of the translocation and the intracellular effector function of secreted virulence factors |
Principal Investigator(s) |
Dehio, Christoph
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Project Members |
Pulliainen, Arto Québatte, Maxime Truttmann, Matthias Muntwiler, Simone Conde Alvarez, Raquel Okujava, Rusudan Mistl, Claudia Engel, Philipp
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Organisation / Research unit |
Departement Biozentrum / Molecular Microbiology (Dehio) |
Project Website |
http://www.biozentrum.unibas.ch/dehio/index.html |
Project start |
01.10.2005 |
Probable end |
30.09.2010 |
Status |
Completed |
Abstract |
Type IV secretion (T4S) is a virulence mechanism shared by several unrelated pathogenic bacteria. By studying T4S in Bartonella we anticipate to provide molecular mechanistic insights into this major virulence mechanism. Based on the subversion of vascular endothelial cell functions by the T4S system of Bartonella, we further expect to contribute new knowledge and tools for the field of vascular biology.
Background The type IV secretion (T4S) systems of gram-negative bacteria mediate the transfer of macromolecular substrates into various target cells, e.g., conjugative DNA transfer into recipient bacteria and intracellular delivery of effector proteins into eukaryotic target cells. Virulence-associated T4S systems are widely distributed among human pathogenic bacteria, including members of the genus Bartonella. These widespread mammalian pathogens typically cause persistent infection of endothelial cells and erythrocytes, which may result in a broad range of clinical manifestations, including fever and hemolytic anemia as the result of erythrocyte invasion, and the formation of vascular tumors due to massive proliferation of endothelial cells. Bartonellae encode two distinct T4S systems which are both essential for pathogenesis. The Trw T4S system is required for erythrocyte infection. In contrast, the VirB/VirD4 T4S system mediates subversion of vascular endothelial cell functions, e.g. in relation to cytoskeleton, inflammation, apoptosis, and proliferation. The latter cellular changes are all dependent on the translocation of seven effector proteins (BepA-BepG). Translocation of these Beps depends on a C-terminal signal, while their N-termini are considered to contribute to effector functions within host cells.
Aims We are studying the Bartonella VirB/VirD4 T4S system and the thereby translocated Bep effector proteins in regard to (i) the molecular interactions of the T4S apparatus with the C-terminal translocation signal of the Beps, and (ii) the effector functions of individual Beps within endothelial cells. We are also testing the suitability of this translocation system for intracellular delivery of heterologous protein and DNA substrates into host cells. In the frame of this project we apply a multidisciplinary approach including bacterial genetics, cell biology, molecular biology, biochemistry, structural biology, genomics, and animal experimentation. The focus of our studies is the structure/function analysis of the Beps, including an interaction analysis (i) with components of the VirB/VirD4 T4S apparatus during translocation into host cells and (ii) with their cellular targets within host cells, which modulate Bep effector functions. |
Keywords |
DNA transfer, bacterial pathogenesis, protein transfer, effector protein, bacterial virulence |
Financed by |
Swiss National Science Foundation (SNSF)
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Published results () |
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ID |
Autor(en) |
Titel |
ISSN / ISBN |
Erschienen in |
Art der Publikation |
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155998 |
Pulliainen, Arto Tapio; Dehio, Christoph |
Bartonella henselae : subversion of vascular endothelial cell functions by translocated bacterial effector proteins |
1357-2725 |
The international journal of biochemistry & cell biology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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155999 |
Rhomberg, Thomas A; Truttmann, Matthias C; Guye, Patrick; Ellner, Yvonne; Dehio, Christoph |
A translocated protein of Bartonella henselae interferes with endocytic uptake of individual bacteria and triggers uptake of large bacterial aggregates via the invasome |
1462-5814 |
Cellular Microbiology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156000 |
Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C |
Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation |
1462-5814 |
Cellular Microbiology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156001 |
Selbach, Matthias; Paul, Florian Ernst; Brandt, Sabine; Guye, Patrick; Daumke, Oliver; Backert, Steffen; Dehio, Christoph; Mann, Matthias |
Host cell interactome of tyrosine-phosphorylated bacterial proteins |
1931-3128 |
Cell Host & Microbe |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156002 |
Engel, P.; Dehio, C. |
Genomics of Host-Restricted Pathogens of the Genus Bartonella |
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Genome dynamics |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156003 |
Llosa, Matxalen; Roy, Craig; Dehio, Christoph |
Bacterial type IV secretion systems in human disease |
0950-382X |
Molecular microbiology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156005 |
Saenz, Henri L; Engel, Philipp; Stoeckli, Michèle C; Lanz, Christa; Raddatz, Günter; Vayssier-Taussat, Muriel; Birtles, Richard; Schuster, Stephan C; Dehio, Christoph |
Genomic analysis of Bartonella identifies type IV secretion systems as host adaptability factors |
1061-4036 |
Nature Genetics |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156006 |
Schmid, M. C.; Scheidegger, F.; Dehio, M.; Balmelle-Devaux, N.; Schulein, R.; Guye, P.; Chennakesava, C. S.; Biedermann, B.; Dehio, C. |
A translocated bacterial protein protects vascular endothelial cells from apoptosis |
1553-7366 ; 1553-7374 |
PLoS Pathogens |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156007 |
de Paz, Héctor D; Sangari, Félix J; Bolland, Silvia; García-Lobo, Juan M; Dehio, Christoph; de la Cruz, Fernando; Llosa, Matxalen |
Functional interactions between type IV secretion systems involved in DNA transfer and virulence |
1350-0872 |
Microbiology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156009 |
Lindroos, Hillevi L; Mira, Alex; Repsilber, Dirk; Vinnere, Olga; Näslund, Kristina; Dehio, Michaela; Dehio, Christoph; Andersson, Siv G E |
Characterization of the genome composition of Bartonella koehlerae by microarray comparative genomic hybridization profiling |
1098-5530 |
Journal of bacteriology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156010 |
Mavris, Maria; Saenz, Henri; Monteil, Martine; Boulouis, Henri-Jean; Dehio, Christoph; Vayssier-Taussat, Muriel |
Characterization of genes involved in long-term bacteremia in mice by Bartonella birtlesii |
0077-8923 |
Annals of the New York Academy of Sciences |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156011 |
Saenz, H. L.; Dehio, C. |
Signature-tagged mutagenesis : technical advances in a negative selection method for virulence gene identification |
1369-5274 ; 1879-0364 |
Current Opinion in Microbiology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156012 |
Dehio, C. |
Bartonella-host-cell interactions and vascular tumour formation |
1740-1526 ; 1740-1534 |
Nature Reviews Microbiology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156013 |
Schröder, Gunnar; Dehio, Christoph |
Virulence-associated type IV secretion systems of Bartonella |
0966-842X |
Trends in microbiology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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156014 |
Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A; Schmid, Michael C; Schröder, Gunnar; Vergunst, Annette C; Carena, Ilaria; Dehio, Christoph |
A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells |
0027-8424 |
Proceedings of the National Academy of Sciences of the United States of America |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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