title: Fatal hemorrhage induced by subtilase cytotoxin from Shiga-toxigenic Escherichia coli.
abstract: Subtilase cytotoxin (SubAB) is an AB(5) type toxin produced by a subset of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum chaperone BiP. The B subunit binds to a receptor on the cell surface. Although SubAB is lethal for mice, the cause of death is not clear. In this study, we demonstrate in mice that SubAB induced small bowel hemorrhage and a coagulopathy characterized by thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time. SubAB also induced inflammatory changes in the small intestine as detected by ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography imaging and histochemical analysis. Using RT-PCR and ELISA, SubAB was shown to increase interleukin-6 in a time-dependent manner. Thus, our results indicate that death in SubAB-treated mice may be associated with severe inflammatory response and hemorrhage of the small intestine, accompanied by coagulopathy and IL6 production.
authors.affiliation: Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Furukawa
authors.forename: Kinnosuke
authors.initials: K
authors.lastname: Yahiro
authors.forename: Atsushi B
authors.initials: AB
authors.lastname: Tsuji
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Terasaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Morinaga
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D006470:Hemorrhage / Q000276:immunology* / Q000382:microbiology / Q000401:mortality*; D006801:Humans; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D054323:Shiga-Toxigenic Escherichia coli / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D013381:Subtilisins / Q000235:genetics / Q000276:immunology*
chemical_list: D029968:Escherichia coli Proteins; D013381:Subtilisins; C527234:subtilase cytotoxin, E coli