title: Inhibition of complement activation by a secreted Staphylococcus aureus protein.
abstract: Staphylococcus aureus can cause a variety of acute and chronic diseases. The ability of S. aureus to cause persistent infections has been linked to its ability to evade or inactivate host immune responses. We have identified a secreted 19-kDa protein produced by S. aureus that binds to the complement protein C3. N-terminal sequencing of this protein identified it as the extracellular fibrinogen-binding protein (Efb). In this study, we demonstrate that Efb can bind to the alpha -chain of C3 and inhibit both the classical and alternative pathways of complement activation. In addition, we show that Efb can inhibit complement-mediated opsonophagocytosis in a dose-dependent manner and that Efb inhibits complement activity by blocking deposition of C3 or by preventing further complement activation beyond C3b. These data suggest that Efb is a virulence factor involved in facilitating persistent S. aureus infections by interfering with complement activity in vivo.
authors.affiliation: Center for Extracellular Matrix Biology, Texas A&M University System Health Science Center, Albert B. Alkek Institute of Biosciences and Technology, Houston, Texas 77030-7552, USA.
authors.forename: Lawrence Y L
authors.initials: LY
authors.lastname: Lee
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.forename: David
authors.initials: D
authors.lastname: Haviland
authors.forename: Rick A
authors.initials: RA
authors.lastname: Wetsel
authors.forename: Edward O
authors.initials: EO
authors.lastname: Yonter
authors.forename: Peter
authors.initials: P
authors.lastname: Syribeys
authors.forename: John
authors.initials: J
authors.lastname: Vernachio
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D009895:Opsonin Proteins / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D003176:Complement C3; C114014:Efb protein, Staphylococcus aureus; D009895:Opsonin Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors