Molecular and cellular basis of the internalization of "Bartonella henselae" by human endothelial cells

Rhomberg, Thomas Alexander. Molecular and cellular basis of the internalization of "Bartonella henselae" by human endothelial cells. 2007, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_7701

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The facultative intracellular bacterium Bartonella henselae enters human
endothelial cells either passively by conventional phagocytosis or actively by a
pathogen-triggered process known as invasome-mediated internalization. The latter
involves the formation of a cell-surface-associated bacterial aggregate, which is
subsequently engulfed by host cell membranes eventually resulting in its complete
Recent work indicated that invasome formation of B. henselae depends on its
VirB/VirD4 T4SS.
This work describes that the VirB/VirD4 T4SS of B. henselae injects a cocktail
of seven effector proteins into endothelial host cells to subvert cellular functions and
that one of these translocated effector proteins, BepG, mediates the sustained
cytoskeletal changes leading to invasome formation. Moreover, this work indicates the
existence of two non-redundant pathways to promote invasome formation, one of
which is governed by the action of BepG and another one, involving further Bep
proteins, which is BepG-independent.
On the host cell side, Rho-family small GTPases Cdc42 and Rac1, but not RhoA
are shown to be required for invasome-mediated internalization. Furthermore, it is
shown that invasome formation leads both to the rearrangement of pre-existing F-actin
fibers and to localized actin polymerization enriched for Arp2/3, which occurs in a
Scar1/WAVE-dependent manner. Finally, this work provides evidence that after
complete internalization the invasome membranes do not fuse with Lamp-1 positive
lysosomes, indicating that invasome-mediated invasion represents a novel mechanism
allowing the uptake of bacteria without entering the endocytic-lysosomal pathway.
Importantly, this is the first report, which attributes the orchestrated action of
more than one effector protein of B. henselae to a known VirB/VirD4 T4SS-dependent
phenotype, namely invasome formation, which represents a multifacetted example for
the complexity of host cell subversion by a bacterial pathogen.
Advisors:Dehio, Christoph
Committee Members:Cornelis, Guy R. and Hall, Michael N.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Dehio, Christoph and Cornelis, Guy R. and Hall, Michael N.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:7701
Thesis status:Complete
Number of Pages:152
Identification Number:
edoc DOI:
Last Modified:22 Jan 2018 15:50
Deposited On:13 Feb 2009 16:26

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