title: Staphylococcal protein Ecb impairs complement receptor-1 mediated recognition of opsonized bacteria.
abstract: Staphyloccus aureus is a major human pathogen leading frequently to sepsis and soft tissue infections with abscesses. Multiple virulence factors including several immune modulating molecules contribute to its survival in the host. When S. aureus invades the human body, one of the first line defenses is the complement system, which opsonizes the bacteria with C3b and attract neutrophils by release of chemotactic peptides. Neutrophils express Complement receptor-1 [CR1, CD35) that interacts with the C3b-opsonized particles and thereby plays an important role in pathogen recognition by phagocytic cells. In this study we observed that a fraction of S. aureus culture supernatant prevented binding of C3b to neutrophils. This fraction consisted of S. aureus leukocidins and Efb. The C-terminus of Efb is known to bind C3b and shares significant sequence homology to the extracellular complement binding protein [Ecb). Here we show that S. aureus Ecb displays various mechanisms to block bacterial recognition by neutrophils. The presence of Ecb blocked direct interaction between soluble CR1 and C3b and reduced the cofactor activity of CR1 in proteolytic inactivation of C3b. Furthermore, Ecb could dose-dependently prevent recognition of C3b by cell-bound CR1 that lead to impaired phagocytosis of NHS-opsonized S. aureus. Phagocytosis was furthermore reduced in the presence of soluble CR1 [sCR1). These data indicate that the staphylococcal protein Ecb prevents recognition of C3b opsonized bacteria by neutrophil CR1 leading to impaired killing by phagocytosis and thereby contribute to immune evasion of S. aureus.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland.
authors.forename: Hanne
authors.initials: H
authors.lastname: Amdahl
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland.
authors.forename: Karita
authors.identifier: http://orcid.org/0000-0002-9619-625X
authors.initials: K
authors.lastname: Haapasalo
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Lydia
authors.initials: L
authors.lastname: Tan
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Taru
authors.initials: T
authors.lastname: Meri
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Division of Clinical Microbiology, Helsinki University Central Hospital Laboratory, Helsinki, Finland.
authors.forename: Pentti I
authors.initials: PI
authors.lastname: Kuusela
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jos A
authors.initials: JA
authors.lastname: van Strijp
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Suzan
authors.initials: S
authors.lastname: Rooijakkers
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland.
authors.forename: T Sakari
authors.initials: TS
authors.lastname: Jokiranta
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D009895:Opsonin Proteins / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011485:Protein Binding; D017463:Receptors, Complement 3b / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D009895:Opsonin Proteins; D017463:Receptors, Complement 3b; D037521:Virulence Factors; C587010:extracellular complement binding protein, Staphylococcus aureus; D003179:Complement C3b