TY - JOUR
T1 - Staphylococcal complement evasion by various convertase-blocking molecules
AU - Jongerius, Ilse
AU - Köhl, Jörg
AU - Pandey, Manoj K.
AU - Ruyken, Maartje
AU - Van Kessel, Kok P.M.
AU - Van Strijp, Jos A.G.
AU - Rooijakkers, Suzan H.M.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - To combat the human immune response, bacteria should be able to divert the effectiveness of the complement system. We identify four potent complement inhibitors in Staphylococcus aureus that are part of a new immune evasion cluster. Two are homologues of the C3 convertase modulator staphylococcal complement inhibitor (SCIN) and function in a similar way as SCIN. Extracellular fibrinogen-binding protein (Efb) and its homologue extracellular complement-binding protein (Ecb) are identified as potent complement evasion molecules, and their inhibitory mechanism was pinpointed to blocking C3b-containing convertases: the alternative pathway C3 convertase C3bBb and the C5 convertases C4b2aC3b and C3b2Bb. The potency of Efb and Ecb to block C5 convertase activity was demonstrated by their ability to block C5a generation and C5a-mediated neutrophil activation in vitro. Further, Ecb blocks C5a-dependent neutrophil recruitment into the peritoneal cavity in a mouse model of immune complex peritonitis. The strong antiinflammatory properties of these novel S. aureus-derived convertase inhibitors make these compounds interesting drug candidates for complement-mediated diseases. JEM
AB - To combat the human immune response, bacteria should be able to divert the effectiveness of the complement system. We identify four potent complement inhibitors in Staphylococcus aureus that are part of a new immune evasion cluster. Two are homologues of the C3 convertase modulator staphylococcal complement inhibitor (SCIN) and function in a similar way as SCIN. Extracellular fibrinogen-binding protein (Efb) and its homologue extracellular complement-binding protein (Ecb) are identified as potent complement evasion molecules, and their inhibitory mechanism was pinpointed to blocking C3b-containing convertases: the alternative pathway C3 convertase C3bBb and the C5 convertases C4b2aC3b and C3b2Bb. The potency of Efb and Ecb to block C5 convertase activity was demonstrated by their ability to block C5a generation and C5a-mediated neutrophil activation in vitro. Further, Ecb blocks C5a-dependent neutrophil recruitment into the peritoneal cavity in a mouse model of immune complex peritonitis. The strong antiinflammatory properties of these novel S. aureus-derived convertase inhibitors make these compounds interesting drug candidates for complement-mediated diseases. JEM
UR - http://www.scopus.com/inward/record.url?scp=34948844450&partnerID=8YFLogxK
U2 - 10.1084/jem.20070818
DO - 10.1084/jem.20070818
M3 - Journal articles
C2 - 17893203
AN - SCOPUS:34948844450
SN - 0022-1007
VL - 204
SP - 2461
EP - 2471
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -