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dc.contributor.authorJagau, Hilger
dc.contributor.authorBehrens, Ina-Kristin
dc.contributor.authorLahme, Karen
dc.contributor.authorLorz, Georgina
dc.contributor.authorKöster, Reinhard W
dc.contributor.authorSchneppenheim, Reinhard
dc.contributor.authorObser, Tobias
dc.contributor.authorBrehm, Maria A
dc.contributor.authorKönig, Gesa
dc.contributor.authorKohler, Thomas P
dc.contributor.authorRohde, Manfred
dc.contributor.authorFrank, Ronald
dc.contributor.authorTegge, Werner
dc.contributor.authorFulde, Marcus
dc.contributor.authorHammerschmidt, Sven
dc.contributor.authorSteinert, Michael
dc.contributor.authorBergmann, Simone
dc.date.accessioned2019-06-11T14:16:28Z
dc.date.available2019-06-11T14:16:28Z
dc.date.issued2019-01-01
dc.identifier.citationFront Microbiol. 2019 Mar 26;10:511. doi: 10.3389/fmicb.2019.00511. eCollection 2019.en_US
dc.identifier.issn1664-302X
dc.identifier.pmid30972039
dc.identifier.doi10.3389/fmicb.2019.00511
dc.identifier.urihttp://hdl.handle.net/10033/621811
dc.description.abstractStreptococcus pneumoniae is a major cause of community acquired pneumonia and septicaemia in humans. These diseases are frequently associated with thromboembolic cardiovascular complications. Pneumococci induce the exocytosis of endothelial Weibel-Palade Bodies and thereby actively stimulate the release of von Willebrand factor (VWF), which is an essential glycoprotein of the vascular hemostasis. Both, the pneumococcus induced pulmonary inflammation and the thromboembolytic complications are characterized by a dysbalanced hemostasis including a marked increase in VWF plasma concentrations. Here, we describe for the first time VWF as a novel interaction partner of capsulated and non-encapsulated pneumococci. Moreover, cell culture infection analyses with primary endothelial cells characterized VWF as bridging molecule that mediates bacterial adherence to endothelial cells in a heparin-sensitive manner. Due to the mechanoresponsive changes of the VWF protein conformation and multimerization status, which occur in the blood stream, we used a microfluidic pump system to generate shear flow-induced multimeric VWF strings on endothelial cell surfaces and analyzed attachment of RFP-expressing pneumococci in flow. By applying immunofluorescence visualization and additional electron microscopy, we detected a frequent and enduring bacterial attachment to the VWF strings. Bacterial attachment to the endothelium was confirmed in vivo using a zebrafish infection model, which is described in many reports and acknowledged as suitable model to study hemostasis mechanisms and protein interactions of coagulation factors. Notably, we visualized the recruitment of zebrafish-derived VWF to the surface of pneumococci circulating in the blood stream and detected a VWF-dependent formation of bacterial aggregates within the vasculature of infected zebrafish larvae. Furthermore, we identified the surface-exposed bacterial enolase as pneumococcal VWF binding protein, which interacts with the VWF domain A1 and determined the binding kinetics by surface plasmon resonance. Subsequent epitope mapping using an enolase peptide array indicates that the peptide 181YGAEIFHALKKILKS195 might serve as a possible core sequence of the VWF interaction site. In conclusion, we describe a VWF-mediated mechanism for pneumococcal anchoring within the bloodstream via surface-displayed enolase, which promotes intravascular bacterial aggregation.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectStreptococcus pneumoniaeen_US
dc.subjectendotheliumen_US
dc.subjectenolaseen_US
dc.subjectvon Willebrand factoren_US
dc.subjectzebrafishen_US
dc.titleVon Willebrand Factor Mediates Pneumococcal Aggregation and Adhesion in Blood Flow.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in Microbiologyen_US
refterms.dateFOA2019-06-11T14:16:29Z
dc.source.journaltitleFrontiers in microbiology


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