Abstract
The complement system is an essential component of host defense against pathogens. Previous research in our laboratory identified StcE, a metalloprotease secreted by
Escherichia coli
O157:H7 that cleaves the serpin C1 esterase inhibitor (C1-INH), a major regulator of the classical complement cascade. Analyses of StcE-treated C1-INH activity revealed that surprisingly, StcE enhanced the ability of C1-INH to inhibit the classical complement-mediated lysis of sheep erythrocytes. StcE directly interacts with both cells and C1-INH, thereby binding C1-INH to the cell surface. This suggests that the augmented activity of StcE-treated C1-INH is due to the increased concentration of C1-INH at the sites of potential lytic complex formation. Indeed, removal of StcE abolishes the ability of C1-INH to bind erythrocyte surfaces, whereas the proteolysis of C1-INH is unnecessary to potentiate its inhibitory activity. Physical analyses showed that StcE interacts with C1-INH within its aminoterminal domain, allowing the unaffected serpin domain to interact with its targets. In addition, StcE-treated C1-INH provides significantly increased serum resistance to
E. coli
K-12 over native C1-INH. These data suggest that by recruiting C1-INH to cell surfaces, StcE may protect both
E. coli
O157:H7 and the host cells to which the bacterium adheres from complement-mediated lysis and potentially damaging inflammatory events.