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dc.contributor.author
Okujava, Rusudan
dc.contributor.author
Guye, Patrick
dc.contributor.author
Lu, Yun-Yueh
dc.contributor.author
Mistl, Claudia
dc.contributor.author
Polus, Florine
dc.contributor.author
Vayssier-Taussat, Muriel
dc.contributor.author
Halin, Cornelia
dc.contributor.author
Rolink, Antonius G.
dc.contributor.author
Dehio, Christoph
dc.date.accessioned
2019-04-05T12:48:47Z
dc.date.available
2017-06-11T11:29:36Z
dc.date.available
2019-04-05T12:48:47Z
dc.date.issued
2014-06-19
dc.identifier.other
10.1371/journal.ppat.1004187
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/87244
dc.identifier.doi
10.3929/ethz-b-000087244
dc.description.abstract
Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions. These effectors may interfere with each other to efficiently control the infection process. Bartonellae are Gram-negative, facultative intracellular bacteria using a VirB type IV secretion system to translocate a cocktail of Bartonella effector proteins (Beps) into host cells. Based on in vitro infection models we demonstrate here that BepE protects infected migratory cells from injurious effects triggered by BepC and is required for in vivo dissemination of bacteria from the dermal site of inoculation to blood. Human endothelial cells (HUVECs) infected with a ΔbepE mutant of B. henselae (Bhe) displayed a cell fragmentation phenotype resulting from Bep-dependent disturbance of rear edge detachment during migration. A ΔbepCE mutant did not show cell fragmentation, indicating that BepC is critical for triggering this deleterious phenotype. Complementation of ΔbepE with BepEBhe or its homologues from other Bartonella species abolished cell fragmentation. This cyto-protective activity is confined to the C-terminal Bartonella intracellular delivery (BID) domain of BepEBhe (BID2.EBhe). Ectopic expression of BID2.EBhe impeded the disruption of actin stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell migration via the RhoA signaling pathway, a major regulator of rear edge retraction. An intradermal (i.d.) model for B. tribocorum (Btr) infection in the rat reservoir host mimicking the natural route of infection by blood sucking arthropods allowed demonstrating a vital role for BepE in bacterial dissemination from derma to blood. While the Btr mutant ΔbepDE was abacteremic following i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored bacteremia. Given that we observed a similar protective effect of BepEBhe on infected bone marrow-derived dendritic cells migrating through a monolayer of lymphatic endothelial cells we propose that infected dermal dendritic cells may be involved in disseminating Bartonella towards the blood stream in a BepE-dependent manner.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science (PLoS)
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
A Translocated Effector Required for Bartonella Dissemination from Derma to Blood Safeguards Migratory Host Cells from Damage by Co-translocated Effectors
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS pathogens
ethz.journal.volume
10
en_US
ethz.journal.issue
6
en_US
ethz.pages.start
e1004187
en_US
ethz.size
19 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
005409548
ethz.publication.place
San Francisco, CA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03816 - Halin Winter, Cornelia / Halin Winter, Cornelia
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03816 - Halin Winter, Cornelia / Halin Winter, Cornelia
ethz.date.deposited
2017-06-11T11:29:59Z
ethz.source
ECIT
ethz.identifier.importid
imp59365223f06b346921
ethz.ecitpid
pub:137318
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T08:34:24Z
ethz.rosetta.lastUpdated
2019-04-05T12:49:02Z
ethz.rosetta.exportRequired
true
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true
ethz.COinS
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