A Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621273
Title:
A Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion.
Authors:
Andritschke, Daniel; Dilling, Sabrina; Emmenlauer, Mario; Welz, Tobias; Schmich, Fabian; Misselwitz, Benjamin; Rämö, Pauli; Rottner, Klemens; Kerkhoff, Eugen; Wada, Teiji; Penninger, Josef M; Beerenwinkel, Niko; Horvath, Peter; Dehio, Christoph; Hardt, Wolf-Dietrich
Abstract:
Salmonella Typhimurium (S. Tm) is a leading cause of diarrhea. The disease is triggered by pathogen invasion into the gut epithelium. Invasion is attributed to the SPI-1 type 3 secretion system (T1). T1 injects effector proteins into epithelial cells and thereby elicits rearrangements of the host cellular actin cytoskeleton and pathogen invasion. The T1 effector proteins SopE, SopB, SopE2 and SipA are contributing to this. However, the host cell factors contributing to invasion are still not completely understood. To address this question comprehensively, we used Hela tissue culture cells, a genome-wide siRNA library, a modified gentamicin protection assay and S. TmSipA, a sopBsopE2sopE mutant which strongly relies on the T1 effector protein SipA to invade host cells. We found that S. TmSipA invasion does not elicit membrane ruffles, nor promote the entry of non-invasive bacteria "in trans". However, SipA-mediated infection involved the SPIRE family of actin nucleators, besides well-established host cell factors (WRC, ARP2/3, RhoGTPases, COPI). Stage-specific follow-up assays and knockout fibroblasts indicated that SPIRE1 and SPIRE2 are involved in different steps of the S. Tm infection process. Whereas SPIRE1 interferes with bacterial binding, SPIRE2 influences intracellular replication of S. Tm. Hence, these two proteins might fulfill non-redundant functions in the pathogen-host interaction. The lack of co-localization hints to a short, direct interaction between S. Tm and SPIRE proteins or to an indirect effect.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
A Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion. 2016, 11 (9):e0161965 PLoS ONE
Journal:
PloS one
Issue Date:
2016
URI:
http://hdl.handle.net/10033/621273
DOI:
10.1371/journal.pone.0161965
PubMed ID:
27627128
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the Research group: molecular cell biology (MZBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorAndritschke, Danielen
dc.contributor.authorDilling, Sabrinaen
dc.contributor.authorEmmenlauer, Marioen
dc.contributor.authorWelz, Tobiasen
dc.contributor.authorSchmich, Fabianen
dc.contributor.authorMisselwitz, Benjaminen
dc.contributor.authorRämö, Paulien
dc.contributor.authorRottner, Klemensen
dc.contributor.authorKerkhoff, Eugenen
dc.contributor.authorWada, Teijien
dc.contributor.authorPenninger, Josef Men
dc.contributor.authorBeerenwinkel, Nikoen
dc.contributor.authorHorvath, Peteren
dc.contributor.authorDehio, Christophen
dc.contributor.authorHardt, Wolf-Dietrichen
dc.date.accessioned2018-02-09T10:41:18Z-
dc.date.available2018-02-09T10:41:18Z-
dc.date.issued2016-
dc.identifier.citationA Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion. 2016, 11 (9):e0161965 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid27627128-
dc.identifier.doi10.1371/journal.pone.0161965-
dc.identifier.urihttp://hdl.handle.net/10033/621273-
dc.description.abstractSalmonella Typhimurium (S. Tm) is a leading cause of diarrhea. The disease is triggered by pathogen invasion into the gut epithelium. Invasion is attributed to the SPI-1 type 3 secretion system (T1). T1 injects effector proteins into epithelial cells and thereby elicits rearrangements of the host cellular actin cytoskeleton and pathogen invasion. The T1 effector proteins SopE, SopB, SopE2 and SipA are contributing to this. However, the host cell factors contributing to invasion are still not completely understood. To address this question comprehensively, we used Hela tissue culture cells, a genome-wide siRNA library, a modified gentamicin protection assay and S. TmSipA, a sopBsopE2sopE mutant which strongly relies on the T1 effector protein SipA to invade host cells. We found that S. TmSipA invasion does not elicit membrane ruffles, nor promote the entry of non-invasive bacteria "in trans". However, SipA-mediated infection involved the SPIRE family of actin nucleators, besides well-established host cell factors (WRC, ARP2/3, RhoGTPases, COPI). Stage-specific follow-up assays and knockout fibroblasts indicated that SPIRE1 and SPIRE2 are involved in different steps of the S. Tm infection process. Whereas SPIRE1 interferes with bacterial binding, SPIRE2 influences intracellular replication of S. Tm. Hence, these two proteins might fulfill non-redundant functions in the pathogen-host interaction. The lack of co-localization hints to a short, direct interaction between S. Tm and SPIRE proteins or to an indirect effect.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshBacterial Proteinsen
dc.subject.meshCell Lineen
dc.subject.meshFluorescent Antibody Techniqueen
dc.subject.meshGenome-Wide Association Studyen
dc.subject.meshHeLa Cellsen
dc.subject.meshHost-Pathogen Interactionsen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshMicrofilament Proteinsen
dc.subject.meshNuclear Proteinsen
dc.subject.meshRNA, Small Interferingen
dc.subject.meshReal-Time Polymerase Chain Reactionen
dc.subject.meshSalmonella typhimuriumen
dc.titleA Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPloS oneen

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