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dc.contributor.author
Di Martino, Maria L.
dc.contributor.author
Ek, Viktor
dc.contributor.author
Hardt, Wolf-Dietrich
dc.contributor.author
Eriksson, Jens
dc.contributor.author
Sellin, Mikael E.
dc.date.accessioned
2019-06-11T11:55:23Z
dc.date.available
2019-06-10T19:18:47Z
dc.date.available
2019-06-11T11:55:23Z
dc.date.issued
2019
dc.identifier.issn
2150-7511
dc.identifier.issn
2161-2129
dc.identifier.other
10.1128/mBio.00603-19
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/346493
dc.identifier.doi
10.3929/ethz-b-000346493
dc.description.abstract
Bacterial host cell invasion mechanisms depend on the bacterium’s virulence factors and the properties of the target cell. The enteropathogen Salmonella enterica serovar Typhimurium (S.Tm) invades epithelial cell types in the gut mucosa and a variety of immune cell types at later infection stages. The molecular mechanism(s) of host cell entry has, however, been studied predominantly in epithelial cell lines. S.Tm uses a type three secretion system (TTSS-1) to translocate effectors into the host cell cytosol, thereby sparking actin ruffle-dependent entry. The ruffles also fuel cooperative invasion by bystander bacteria. In addition, several TTSS-1-independent entry mechanisms exist, involving alternative S.Tm virulence factors, or the passive uptake of bacteria by phagocytosis. However, it remains ill-defined how S.Tm invasion mechanisms vary between host cells. Here, we developed an internally controlled and scalable method to map S.Tm invasion mechanisms across host cell types and conditions. The method relies on host cell infections with consortia of chromosomally tagged wild-type and mutant S.Tm strains, where the abundance of each strain can be quantified by qPCR or amplicon sequencing. Using this methodology, we quantified cooccurring TTSS-1-dependent, cooperative, and TTSS-1-independent invasion events in epithelial, monocyte, and macrophage cells. We found S.Tm invasion of epithelial cells and monocytes to proceed by a similar MOI-dependent mix of TTSS-1-dependent and cooperative mechanisms. TTSS-1-independent entry was more frequent in macrophages. Still, TTSS-1-dependent invasion dominated during the first minutes of interaction also with this cell type. Finally, the combined action of the SopB/SopE/SopE2 effectors was sufficient to explain TTSS-1-dependent invasion across both epithelial and phagocytic cells.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
American Society for Microbiology
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Salmonella
en_US
dc.subject
bacterial invasion
en_US
dc.subject
genome barcoding
en_US
dc.subject
epithelial cells
en_US
dc.subject
macrophages
en_US
dc.subject
monocytes
en_US
dc.title
Barcoded Consortium Infections Resolve Cell Type-Dependent Salmonella enterica Serovar Typhimurium Entry Mechanisms
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-05-21
ethz.journal.title
mBio
ethz.journal.volume
10
en_US
ethz.journal.issue
3
en_US
ethz.pages.start
00603-19
en_US
ethz.size
15 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
ethz.date.deposited
2019-06-10T19:19:11Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-06-11T11:55:35Z
ethz.rosetta.lastUpdated
2021-02-15T04:45:26Z
ethz.rosetta.versionExported
true
ethz.COinS
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