| Escherichia coli O157:H7 is a human pathogen that causes diarrhea, hemorrhagic colitis, and the potentially lethal hemolytic uremic syndrome. We have identified a secreted protease of previously unknown function encoded on the pO157 virulence plasmid of E. coli O157:H7, which cleaves the critical regulator C1 esterase inhibitor (C1-INH), a member of the serine protease inhibitor (serpin) family. The protein, named StcE for s&barbelow;ecreted prot&barbelow;ease of C&barbelow;1 esterase inhibitor from E&barbelow;HEC, cleaves within the heavily glycosylated amino terminal domain of C1-INH to produce ∼60–65 kDa fragments. StcE does not digest other serine protease inhibitors, extracellular matrix proteins, or universal protease targets. Surprisingly, StcE enhances the ability of C1-INH to inhibit the classical complement pathway by localizing C1-INH to cell surfaces, thereby increasing the concentration of the serpin at sites of potential lytic complex formation. In addition, StcE-treated C1-INH provides increased serum resistance to E. coli K–12 over native C1-INH. We also observed that StcE causes the aggregation of cultured human T cells, which may impede their migration through the vascular endothelium. StcE antigen and activity were detected in the feces of a child with an E. coli O157:H7 infection, demonstrating the expression of StcE during human disease. StcE is broadly distributed among E. coli strains of the EHEC 1 complex and was acquired at an early stage in the evolution of O157:H7 from its enteropathogenic O55:H7 ancestor, prior to the acquisition of other plasmid-borne virulence factors and the Shiga toxin. The potentiation of C1-INH activity by StcE may play a role in E. coli O157:H7 serum resistance and/or the protection of the enterocytes to which the bacterium adheres, suggesting a mechanism for bacterial survival in vivo. |
