Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases.
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.
Rooijakkers
Suzan H M
SH
Eijkman Winkler Institute, University Medical Center Utrecht, G04.614, 3584 CX Utrecht, The Netherlands. s.h.m.rooijakkers@azu.nl
Ruyken
Maartje
M
Roos
Anja
A
Daha
Mohamed R
MR
Presanis
Julia S
JS
Sim
Robert B
RB
van Wamel
Willem J B
WJ
van Kessel
Kok P M
KP
van Strijp
Jos A G
JA
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
D001426:Bacterial Proteins; D003169:Complement Inactivator Proteins; D010446:Peptide Fragments; D003179:Complement C3b; D003165:Complement System Proteins; D051561:Complement C3 Convertase, Alternative Pathway