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

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

研究成果: Article査読

5 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号10776
ジャーナルScientific reports
8
1
DOI
出版ステータスPublished - 2018 12 1

ASJC Scopus subject areas

  • General

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