StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor.
Escherichia coli O157:H7 causes diarrhoea, haemorrhagic colitis, and the haemolytic uraemic syndrome. We have identified a protein of previously unknown function encoded on the pO157 virulence plasmid of E. coli O157:H7, which is the first described protease that specifically cleaves C1 esterase inhibitor (C1-INH), a member of the serine protease inhibitor family. The protein, named StcE for secreted protease of C1 esterase inhibitor from EHEC (formerly Tagn), cleaves C1-INH to produce (unique) approximately 60-65 kDa fragments. StcE does not digest other serine protease inhibitors, extracellular matrix proteins or universal protease targets. We also observed that StcE causes the aggregation of cultured human T cells but not macrophage-like cells or B cells. Substitution of aspartic acid for glutamic acid at StcE position 435 within the consensus metalloprotease active site ablates its abilities to digest C1-INH and to aggregate T cells. StcE is secreted by the etp type II secretion pathway encoded on pO157, and extracellular StcE levels are positively regulated by the LEE-encoded regulator, Ler. StcE antigen and activity were detected in the faeces of a child with an E. coli O157:H7 infection, demonstrating the expression of StcE during human disease. Cleavage of C1-INH by StcE could plausibly cause localized pro-inflammatory and coagulation responses resulting in tissue damage, intestinal oedema and thrombotic abnormalities.
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA.
Wyndham W
WW
Lathem
Thomas E
TE
Grys
Sarah E
SE
Witowski
Alfredo G
AG
Torres
James B
JB
Kaper
Phillip I
PI
Tarr
Rodney A
RA
Welch
D001798:Blood Proteins / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002648:Child; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D016384:Consensus Sequence; D003967:Diarrhea / Q000382:microbiology; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D005243:Feces / Q000382:microbiology; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects; D015534:Trans-Activators / Q000502:physiology; D014774:Virulence
D001798:Blood Proteins; D003174:Complement C1 Inactivator Proteins; D029968:Escherichia coli Proteins; C465556:Ler protein, E coli; D015534:Trans-Activators; D008666:Metalloendopeptidases; C465555:StcE protein, E coli