Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7

被引:52
作者
Lathem, WW [1 ]
Bergsbaken, T [1 ]
Welch, RA [1 ]
机构
[1] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA
关键词
complement; serpins; serum resistance; contact activation; reactive center loop;
D O I
10.1084/jem.20030255
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 cell's to which the bacterium adheres from complement-mediated lysis and potentially damaging inflammatory events.
引用
收藏
页码:1077 / 1087
页数:11
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