ESPP, A NOVEL EXTRACELLULAR SERINE-PROTEASE OF ENTEROHEMORRHAGIC ESCHERICHIA-COLI O157-H7 CLEAVES HUMAN COAGULATION-FACTOR-V

In this study, we identified and characterized a novel secreted protei n, the extracellular serine protease EspP, which is encoded by the lar ge plasmid of enterohaemorrhagic Escherichia coil (EHEC) O157:H7. The corresponding espP gene consists of a 3900 bp open reading frame that is able to encode a 1300-amino-acid protein. EspP is synthesized as a large precursor which is then processed at the N- and C-termini during secretion. It can be grouped into the autotransporter protein family. The deduced amino acid sequence of EspP showed homology to several se creted or surface-exposed proteins of pathogenic bacteria, in particul ar EspC of enteropathogenic E. coli and IgA1 proteases from Neisseria spp. and Haemophilus influenzae. Hybridization experiments and immunob lot analysis of clinical EHEC isolates showed that EspP is widespread among EHEC of the serogroup O157 and that it also exists in serogroup O26. A specific immune response against EspP was detected in sera from patients suffering from EHEC infections. Functional analysis showed t hat EspP is a protease capable of cleaving pepsin A and human coagulat ion factor V. Degradation of factor V could contribute to the mucosal haemorrhage observed in patients with haemorrhagic colitis.