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Published 19 April 2004. doi:10.1084/jem.20030255
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 8, 1077-1087
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Potentiation of C1 Esterase Inhibitor by StcE, a Metalloprotease Secreted by Escherichia coli O157:H7

Wyndham W. Lathem, Tessa Bergsbaken, and Rodney A. Welch

Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706

Address correspondence to Rodney A. Welch, Department of Medical Microbiology and Immunology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706. Phone: (608) 263-2700; Fax: (608) 262-8418; email: rawelch{at}wisc.edu

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.

Key Words: complement • serpins • serum resistance • contact activation • reactive center loop

W.W. Lathem's present address is Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Ave., Saint Louis, MO 63110.

T. Bergsbaken's present address is Department of Microbiology, University of Washington, 1959 NE Pacific St., Seattle, WA 98195.

Abbreviations used in this paper: C1-INH, C1 esterase inhibitor; LB, Luria-Bertani; RCL, reactive center loop.


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