Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface

• Published in: PLoS pathogens 2013-12, Vol.9 (12), p.e1003816-e1003816
• Main Authors: Ko, Ya-Ping, Kuipers, Annemarie, Freitag, Claudia M, Jongerius, Ilse, Medina, Eva, van Rooijen, Willemien J, Spaan, András N, van Kessel, Kok P M, Höök, Magnus, Rooijakkers, Suzan H M
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Bacterial infections; Bacterial proteins; Bacterial Proteins - metabolism; Bacteriology; Binding sites; Blood Coagulation Factors - metabolism; Cells, Cultured; Coagulation; Complement C3b - metabolism; Enzymes; Experiments; Female; Fibrinogen - metabolism; Health aspects; Host-parasite relationships; Humans; Immune Evasion; Medical research; Medicine, Experimental; Mice; Mice, Inbred C57BL; Nosocomial infections; Phagocytosis; Phagocytosis - immunology; Physiological aspects; Protein Binding; Proteins; Staphylococcal Infections - immunology; Staphylococcal Infections - metabolism; Staphylococcus aureus; Staphylococcus aureus - immunology; Staphylococcus aureus - metabolism; Staphylococcus infections; Transmission electron microscopy
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003816

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.