title: Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases.
abstract: The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b deposition on activator surfaces. Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus aureus by human neutrophils. As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule.
authors.affiliation: Eijkman Winkler Institute, University Medical Center Utrecht, G04.614, 3584 CX Utrecht, The Netherlands. s.h.m.rooijakkers@azu.nl
authors.forename: Suzan H M
authors.initials: SH
authors.lastname: Rooijakkers
authors.forename: Maartje
authors.initials: M
authors.lastname: Ruyken
authors.forename: Anja
authors.initials: A
authors.lastname: Roos
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Julia S
authors.initials: JS
authors.lastname: Presanis
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Willem J B
authors.initials: WJ
authors.lastname: van Wamel
authors.forename: Kok P M
authors.initials: KP
authors.lastname: van Kessel
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism*; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000378:metabolism*; D003169:Complement Inactivator Proteins / Q000276:immunology* / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D010446:Peptide Fragments / Q000378:metabolism*; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003169:Complement Inactivator Proteins; D010446:Peptide Fragments; D003179:Complement C3b; D003165:Complement System Proteins; D051561:Complement C3 Convertase, Alternative Pathway