4.5 Article

Fatal hemorrhage induced by subtilase cytotoxin from Shiga-toxigenic Escherichia coli

Journal

MICROBIAL PATHOGENESIS
Volume 50, Issue 3-4, Pages 159-167

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.micpath.2011.01.002

Keywords

Subtilase cytotoxin; Hemorrhage; Coagulopathy; Inflammation

Funding

  1. Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology
  2. Japanese Government
  3. Japan Science and Technology Agency
  4. NIH, NHLBI

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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 F-18-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. (C) 2011 Elsevier Ltd. All rights reserved.

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