Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7.
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.
Lathem
Wyndham W
WW
Department of Medical Microbiology and Immunology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Bergsbaken
Tessa
T
Welch
Rodney A
RA
D000818:Animals; D019556:COS Cells; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage* / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000187:drug effects; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D019453:Escherichia coli O157 / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000008:administration & dosage*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000008:administration & dosage*; D008954:Models, Biological; D012756:Sheep
D003174:Complement C1 Inactivator Proteins; D029968:Escherichia coli Proteins; D008666:Metalloendopeptidases; C465555:StcE protein, E coli