Potentiation of C1 Esterase Inhibitor by StcE, a Metalloprotease Secreted by Escherichia coli O157:H7

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1077-1087
Number of pages11
JournalJournal of Experimental Medicine
Volume199
Issue number8
DOIs
StatePublished - Apr 19 2004

Keywords

  • Complement
  • Contact activation
  • Reactive center loop
  • Serpins
  • Serum resistance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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