Exosome-associated Shiga toxin 2 is released from cells and causes severe toxicity in mice View Full Text


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Article Info

DATE

2018-07-17

AUTHORS

Miho Watanabe-Takahashi, Shinji Yamasaki, Masayuki Murata, Fumi Kano, Jun Motoyama, Jyoji Yamate, Jumpei Omi, Waka Sato, Hirofumi Ukai, Kentaro Shimasaki, Masaya Ikegawa, Miwa Tamura-Nakano, Ryohei Yanoshita, Yuri Nishino, Atsuo Miyazawa, Yasuhiro Natori, Noriko Toyama-Sorimachi, Kiyotaka Nishikawa

ABSTRACT

Shiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), is classified into two subgroups, Stx1 and Stx2. Clinical data clearly indicate that Stx2 is associated with more severe toxicity than Stx1, but the molecular mechanism underlying this difference is not fully understood. Here, we found that after being incorporated into target cells, Stx2, can be transported by recycling endosomes, as well as via the regular retrograde transport pathway. However, transport via recycling endosome did not occur with Stx1. We also found that Stx2 is actively released from cells in a receptor-recognizing B-subunit dependent manner. Part of the released Stx2 is associated with microvesicles, including exosome markers (referred to as exo-Stx2), whose origin is in the multivesicular bodies that formed from late/recycling endosomes. Finally, intravenous administration of exo-Stx2 to mice causes more lethality and tissue damage, especially severe renal dysfunction and tubular epithelial cell damage, compared to a free form of Stx2. Thus, the formation of exo-Stx2 might contribute to the severity of Stx2 in vivo, suggesting new therapeutic strategies against EHEC infections. More... »

PAGES

10776

References to SciGraph publications

  • 2009-12-21. Shiga toxins — from cell biology to biomedical applications in NATURE REVIEWS MICROBIOLOGY
  • 2013-06-14. Retrograde transport of protein toxins through the Golgi apparatus in HISTOCHEMISTRY AND CELL BIOLOGY
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  • 2009-12-06. Rab27a and Rab27b control different steps of the exosome secretion pathway in NATURE CELL BIOLOGY
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  • 2012-02-04. Microvesicles in Health and Disease in ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS
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  • 1992-08. Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum in NATURE
  • Journal

    TITLE

    Scientific Reports

    ISSUE

    1

    VOLUME

    8

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-29128-9

    DOI

    http://dx.doi.org/10.1038/s41598-018-29128-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1105534062

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30018364


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    361 grid-institutes:grid.440938.2 schema:alternateName Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo, Japan
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