Phagocytosis Escape by a Staphylococcus aureus Protein That Connects Complement and Coagulation Proteins at the Bacterial Surface.

2.50
Hdl Handle:
http://hdl.handle.net/10033/311059
Title:
Phagocytosis Escape by a Staphylococcus aureus Protein That Connects Complement and Coagulation Proteins at the Bacterial Surface.
Authors:
Ko, Ya-Ping; Kuipers, Annemarie; Freitag, Claudia M; Jongerius, Ilse; Medina, Eva ( 0000-0001-9073-0223 ) ; van Rooijen, Willemien J; Spaan, András N; van Kessel, Kok P M; Höök, Magnus; Rooijakkers, Suzan H M
Abstract:
Upon contact with human plasma, bacteria are rapidly recognized by the complement system that labels their surface for uptake and clearance by phagocytic cells. Staphylococcus aureus secretes the 16 kD Extracellular fibrinogen binding protein (Efb) that binds two different plasma proteins using separate domains: the Efb N-terminus binds to fibrinogen, while the C-terminus binds complement C3. In this study, we show that Efb blocks phagocytosis of S. aureus by human neutrophils. In vitro, we demonstrate that Efb blocks phagocytosis in plasma and in human whole blood. Using a mouse peritonitis model we show that Efb effectively blocks phagocytosis in vivo, either as a purified protein or when produced endogenously by S. aureus. Mutational analysis revealed that Efb requires both its fibrinogen and complement binding residues for phagocytic escape. Using confocal and transmission electron microscopy we show that Efb attracts fibrinogen to the surface of complement-labeled S. aureus generating a 'capsule'-like shield. This thick layer of fibrinogen shields both surface-bound C3b and antibodies from recognition by phagocytic receptors. This information is critical for future vaccination attempts, since opsonizing antibodies may not function in the presence of Efb. Altogether we discover that Efb from S. aureus uniquely escapes phagocytosis by forming a bridge between a complement and coagulation protein.
Affiliation:
RG Infection immunology, Helmholtz Centre for infection research (HZI), Inhoffenstr. 7, D-38125 Braunschweig, Germany
Citation:
Phagocytosis Escape by a Staphylococcus aureus Protein That Connects Complement and Coagulation Proteins at the Bacterial Surface. 2013, 9 (12):e1003816 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Dec-2013
URI:
http://hdl.handle.net/10033/311059
DOI:
10.1371/journal.ppat.1003816
PubMed ID:
24348255
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the research group immunology of infection (INI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKo, Ya-Pingen
dc.contributor.authorKuipers, Annemarieen
dc.contributor.authorFreitag, Claudia Men
dc.contributor.authorJongerius, Ilseen
dc.contributor.authorMedina, Evaen
dc.contributor.authorvan Rooijen, Willemien Jen
dc.contributor.authorSpaan, András Nen
dc.contributor.authorvan Kessel, Kok P Men
dc.contributor.authorHöök, Magnusen
dc.contributor.authorRooijakkers, Suzan H Men
dc.date.accessioned2014-01-08T09:58:11Zen
dc.date.available2014-01-08T09:58:11Zen
dc.date.issued2013-12en
dc.identifier.citationPhagocytosis Escape by a Staphylococcus aureus Protein That Connects Complement and Coagulation Proteins at the Bacterial Surface. 2013, 9 (12):e1003816 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid24348255en
dc.identifier.doi10.1371/journal.ppat.1003816en
dc.identifier.urihttp://hdl.handle.net/10033/311059en
dc.description.abstractUpon contact with human plasma, bacteria are rapidly recognized by the complement system that labels their surface for uptake and clearance by phagocytic cells. Staphylococcus aureus secretes the 16 kD Extracellular fibrinogen binding protein (Efb) that binds two different plasma proteins using separate domains: the Efb N-terminus binds to fibrinogen, while the C-terminus binds complement C3. In this study, we show that Efb blocks phagocytosis of S. aureus by human neutrophils. In vitro, we demonstrate that Efb blocks phagocytosis in plasma and in human whole blood. Using a mouse peritonitis model we show that Efb effectively blocks phagocytosis in vivo, either as a purified protein or when produced endogenously by S. aureus. Mutational analysis revealed that Efb requires both its fibrinogen and complement binding residues for phagocytic escape. Using confocal and transmission electron microscopy we show that Efb attracts fibrinogen to the surface of complement-labeled S. aureus generating a 'capsule'-like shield. This thick layer of fibrinogen shields both surface-bound C3b and antibodies from recognition by phagocytic receptors. This information is critical for future vaccination attempts, since opsonizing antibodies may not function in the presence of Efb. Altogether we discover that Efb from S. aureus uniquely escapes phagocytosis by forming a bridge between a complement and coagulation protein.en
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen
dc.titlePhagocytosis Escape by a Staphylococcus aureus Protein That Connects Complement and Coagulation Proteins at the Bacterial Surface.en
dc.typeArticleen
dc.contributor.departmentRG Infection immunology, Helmholtz Centre for infection research (HZI), Inhoffenstr. 7, D-38125 Braunschweig, Germanyen
dc.identifier.journalPLoS pathogensen

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