INHIBITION OF THE HEMOLYTIC-ACTIVITY OF THE FIRST COMPONENT OF COMPLEMENT C1 BY AN ESCHERICHIA-COLI C1Q BINDING-PROTEIN

Molecular mimicry is a well established mechanism via which bacteria p rotect themselves from complement-mediated killing. We have previously demonstrated that a number of human cells express receptors for C1q ( C1qR) and that the soluble form of this receptor inhibits activation o f the classical pathway of complement. We now investigated whether Esc herichia coli possesses a C1qR-like protein that protects these bacter ia from complement-mediated injury. By FAGS analysis it was shown that approximately 60% of the bacteria bound C1q directly in the absence o f Abs. With ELISA we confirmed that the bacterial cell envelope was ab le to bind C1q in a dose-dependent fashion. We isolated a cell envelop e associated C1q binding protein (C1qBP) by C1q affinity chromatograph y, then by anion exchange chromatography and gel filtration chromatogr aphy. On SDS-PAGE, the m.w. of C1qBP appeared to be 57 kDa and 51 kDa under reducing and nonreducing conditions, respectively, It was demons trated that C1qBP specifically binds C1q and inhibits the hemolytic ac tivity of C1q in both a dose- acid time dependent fashion. The binding of C1qBP to C1q is inhibited by C1q itself and also by the collagen-l ike stalks and the globular heads of C1q. In this respect, bacterial C 1qBP is different from human C1qR because the binding of C1q to C1qR i s only inhibited by the collagen-like stalks of C1q and not by the glo bular heads of C1q, C1qBP, when bound to C1q, prevents the assembly wi th C1r and C1s to form a functional C1 complex. The occurrence of C1qB P is not limited to certain E. coli strains, but is also found on Stap hylococcus aureus, Citrobacter freundii, and Pseudomonas aeroginosa. A lso, the binding of I-125-labeled C1q to these bacteria is specific be cause the binding of C1q to these bacteria is inhibitable with isolate d soluble C1qBP. These findings provide evidence for the existence of a C1qR-like protein on bacteria that might protect them from complemen t-mediated damage.