title: Staphylococcal Ecb protein and host complement regulator factor H enhance functions of each other in bacterial immune evasion.
abstract: Staphylococcus aureus is a major human pathogen causing more than a tenth of all septicemia cases and often superficial and deep infections in various tissues. One of the immune evasion strategies of S. aureus is to secrete proteins that bind to the central complement opsonin C3b. One of these, extracellular complement binding protein (Ecb), is known to interfere directly with functions of C3b. Because C3b is also the target of the physiological plasma complement regulator, factor H (FH), we studied the effect of Ecb on the complement regulatory functions of FH. We show that Ecb enhances acquisition of FH from serum onto staphylococcal surfaces. Ecb and FH enhance mutual binding to C3b and also the function of each other in downregulating complement activation. Both Ecb and the C-terminal domains 19-20 of FH bind to the C3d part of C3b. We show that the mutual enhancing effect of Ecb and FH on binding to C3b depends on binding of the FH domain 19 to the C3d part of C3b next to the binding site of Ecb on C3d. Our results show that Ecb, FH, and C3b form a tripartite complex. Upon exposure of serum-sensitive Haemophilus influenzae to human serum, Ecb protected the bacteria, and this effect was enhanced by the addition of the C-terminal domains 19-20 of FH. This finding indicates that the tripartite complex formation could give additional protection to bacteria and that S. aureus is thereby able to use host FH and bacterial Ecb in a concerted action to eliminate C3b at the site of infection.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, Research Programs Unit, Immunobiology, University of Helsinki, FIN-00014 Helsinki, Finland.
authors.forename: Hanne
authors.initials: H
authors.lastname: Amdahl
authors.forename: Ilse
authors.initials: I
authors.lastname: Jongerius
authors.forename: Taru
authors.initials: T
authors.lastname: Meri
authors.forename: Tanja
authors.initials: T
authors.lastname: Pasanen
authors.forename: Satu
authors.initials: S
authors.lastname: Hyvärinen
authors.forename: Karita
authors.initials: K
authors.lastname: Haapasalo
authors.forename: Jos A
authors.initials: JA
authors.lastname: van Strijp
authors.forename: Suzan H
authors.initials: SH
authors.lastname: Rooijakkers
authors.forename: T Sakari
authors.initials: TS
authors.lastname: Jokiranta
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D001665:Binding Sites; D003179:Complement C3b / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D017242:Complement Factor H / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003169:Complement Inactivator Proteins / Q000737:chemistry / Q000502:physiology*; D003170:Complement Pathway, Alternative; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007113:Immunity, Innate; D008958:Models, Molecular; D046912:Multiprotein Complexes; D010446:Peptide Fragments / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D044967:Serum / Q000276:immunology; D013203:Staphylococcal Infections; D013211:Staphylococcus aureus / Q000276:immunology*; D037521:Virulence Factors / Q000737:chemistry / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D003169:Complement Inactivator Proteins; C114014:Efb protein, Staphylococcus aureus; C524396:Ehp protein, Staphylococcus aureus; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D037521:Virulence Factors; C587010:extracellular complement binding protein, Staphylococcus aureus; D003179:Complement C3b; D017242:Complement Factor H