StcE, a metalloprotease secreted by Escherichia coli O157

H7, specifically cleaves C1 esterase inhibitor

Wyndham W. Lathem, Thomas E. Grys, Sarah E. Witowski, Alfredo Torres, James B. Kaper, Phillip I. Tarr, Rodney A. Welch

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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) ≈ 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 theetp 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.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalMolecular Microbiology
Volume45
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

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Complement C1 Inhibitor Protein
Escherichia coli O157
Metalloproteases
Serine Proteinase Inhibitors
Peptide Hydrolases
T-Lymphocytes
Hemolytic-Uremic Syndrome
Extracellular Matrix Proteins
Secretory Pathway
Colitis
Aspartic Acid
Feces
Virulence
Glutamic Acid
Diarrhea
Edema
Catalytic Domain
Proteins
Plasmids
B-Lymphocytes

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

StcE, a metalloprotease secreted by Escherichia coli O157 : H7, specifically cleaves C1 esterase inhibitor. / Lathem, Wyndham W.; Grys, Thomas E.; Witowski, Sarah E.; Torres, Alfredo; Kaper, James B.; Tarr, Phillip I.; Welch, Rodney A.

In: Molecular Microbiology, Vol. 45, No. 2, 2002, p. 277-288.

Research output: Contribution to journalArticle

Lathem, Wyndham W. ; Grys, Thomas E. ; Witowski, Sarah E. ; Torres, Alfredo ; Kaper, James B. ; Tarr, Phillip I. ; Welch, Rodney A. / StcE, a metalloprotease secreted by Escherichia coli O157 : H7, specifically cleaves C1 esterase inhibitor. In: Molecular Microbiology. 2002 ; Vol. 45, No. 2. pp. 277-288.
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