Abstract
Members of a family of collagen-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) from Gram-positive bacteria are established virulence factors in several infectious diseases models. Here, we report that these adhesins also can bind C1q and act as inhibitors of the classical complement pathway. Molecular analyses of Cna from Staphylococcus aureus suggested that this prototype MSCRAMM bound to the collagenous domain of C1q and interfered with the interactions of C1r with C1q. As a result, C1r2C1s2 was displaced from C1q, and the C1 complex was deactivated. This novel function of the Cna-like MSCRAMMs represents a potential immune evasion strategy that could be used by numerous Gram-positive pathogens.
Highlights
Collagen-binding MSCRAMMs from Gram-positive bacteria are adhesins and are virulence factors in several infectious diseases models
The ability of Cna to interact with C1q in the presence of serum was evaluated in an ELISA in which Cna-coated wells were incubated with normal human serum (NHS) or C1q-depleted serum (C1q-dpl) serum, and bound C1q was detected by polyclonal anti-C1q antibody
The fact that the C1 complex exhibits a higher affinity for immune complexes than does isolated C1q supports the idea that two distinct conformational states with different binding properties exist for C1q in these two conditions (32), and our results indicate that Cna binding to the C1q subunit may stabilize the conformation of C1q that has a low affinity for immune complexes
Summary
Collagen-binding MSCRAMMs from Gram-positive bacteria are adhesins and are virulence factors in several infectious diseases models. Members of the Cna-like family of collagen-binding MSCRAMMs are structurally related (Fig. 1) and are found in many Gram-positive bacterial species, e.g. Ace in Enterococcus faecalis (12), Acm in Enterococcus faecium (13), Cne in Streptococcus equi (14), and Cnm in Streptococcus mutans (15) These collagen-binding MSCRAMMs are virulence factors in several animal models of infectious diseases (16 –22) and can function as adhesins and mediate bacterial attachment to collagen-rich tissues. In this communication, we report that the Cna-like family of collagen-binding MSCRAMMs bind C1q and inhibit the complement classical pathway activation. The molecular bases for this inhibition are dissected and described
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