Scholarlink

<p>Botulinum toxins (BoNTs) produced by <i>Clostridium botulinum</i> are the most potent known bacterial toxins. The BoNT complex from serotype B-Okra (LPTC/B<sup>Okra</sup>) exerts at least 80-fold higher oral toxicity in mice compared with that from serotype A1 (L-PTC/A<sup>62A</sup>). Here, we show that L-PTC/B<sup>Okra</sup> is predominantly absorbed through enterocytes, whereas LPTC/A<sup>62A</sup> targets intestinal microfold cells. Furthermore, α1,2-fucosylation of intestinal mucin determines the oral toxicity of L-PTCs as well as their entry routes, due to differential carbohydrate-binding spectrum of one of the L-PTC components, the hemagglutinin (HA) complex. Fucosylation-deficient mice display reduced intestinal mucin penetration of L-PTC/B<sup>Okra</sup> via HA, and lower susceptibility to oral intoxication with this toxin. Thus, our results shed light on the molecular mechanisms by which the oral toxicity of BoNTs is increased after crossing intestinal mucus layers</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Gut mucin fucosylation dictates the entry of botulinum toxin complexes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月25日

查看全文
  • Sho Amatsu,
  • Takuhiro Matsumura,
  • Chiyono Morimoto,
  • Sunanda Keisham,
  • Yoshiyuki Goto,
  • Tomoko Kohda,
  • Jun Hirabayashi,
  • Kengo Kitadokoro,
  • Takane Katayama,
  • Hiroshi Kiyono,
  • Hiroaki Tateno,
  • Masahiko Zuka,
  • Yukako Fujinaga

摘要

Botulinum toxins (BoNTs) produced by Clostridium botulinum are the most potent known bacterial toxins. The BoNT complex from serotype B-Okra (LPTC/BOkra) exerts at least 80-fold higher oral toxicity in mice compared with that from serotype A1 (L-PTC/A62A). Here, we show that L-PTC/BOkra is predominantly absorbed through enterocytes, whereas LPTC/A62A targets intestinal microfold cells. Furthermore, α1,2-fucosylation of intestinal mucin determines the oral toxicity of L-PTCs as well as their entry routes, due to differential carbohydrate-binding spectrum of one of the L-PTC components, the hemagglutinin (HA) complex. Fucosylation-deficient mice display reduced intestinal mucin penetration of L-PTC/BOkra via HA, and lower susceptibility to oral intoxication with this toxin. Thus, our results shed light on the molecular mechanisms by which the oral toxicity of BoNTs is increased after crossing intestinal mucus layers