Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity

Takuhiro Matsumura, Yo Sugawara, Masahiro Yutani, Sho Amatsu, Hideo Yagita, Tomoko Kohda, Shin Ichi Fukuoka, Yutaka Nakamura, Shinji Fukuda, Kouji Hase, Hiroshi Ohno, Yukako Fujinaga

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

To cause food-borne botulism, botulinum neurotoxin (BoNT) in the gastrointestinal lumen must traverse the intestinal epithelial barrier. However, the mechanism by which BoNT crosses the intestinal epithelial barrier remains unclear. BoNTs are produced along with one or more non-toxic components, with which they form progenitor toxin complexes (PTCs). Here we show that serotype A1 L-PTC, which has high oral toxicity and makes the predominant contribution to causing illness, breaches the intestinal epithelial barrier from microfold (M) cells via an interaction between haemagglutinin (HA), one of the non-toxic components, and glycoprotein 2 (GP2). HA strongly binds to GP2 expressed on M cells, which do not have thick mucus layers. Susceptibility to orally administered L-PTC is dramatically reduced in M-cell-depleted mice and GP2-deficient (Gp2-/-) mice. Our finding provides the basis for the development of novel antitoxin therapeutics and delivery systems for oral biologics.

Original languageEnglish
Article number6255
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015 Feb 17

Fingerprint

Type A Botulinum Toxins
Glycoproteins
Neurotoxins
Hemagglutinins
mice
cells
mucus
Antitoxins
Botulism
lumens
Mucus
Biological Products
food
Cell Communication
toxicity
Toxicity
delivery
magnetic permeability
Food
causes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Matsumura, T., Sugawara, Y., Yutani, M., Amatsu, S., Yagita, H., Kohda, T., ... Fujinaga, Y. (2015). Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity. Nature Communications, 6, [6255]. https://doi.org/10.1038/ncomms7255

Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity. / Matsumura, Takuhiro; Sugawara, Yo; Yutani, Masahiro; Amatsu, Sho; Yagita, Hideo; Kohda, Tomoko; Fukuoka, Shin Ichi; Nakamura, Yutaka; Fukuda, Shinji; Hase, Kouji; Ohno, Hiroshi; Fujinaga, Yukako.

In: Nature Communications, Vol. 6, 6255, 17.02.2015.

Research output: Contribution to journalArticle

Matsumura, T, Sugawara, Y, Yutani, M, Amatsu, S, Yagita, H, Kohda, T, Fukuoka, SI, Nakamura, Y, Fukuda, S, Hase, K, Ohno, H & Fujinaga, Y 2015, 'Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity', Nature Communications, vol. 6, 6255. https://doi.org/10.1038/ncomms7255
Matsumura, Takuhiro ; Sugawara, Yo ; Yutani, Masahiro ; Amatsu, Sho ; Yagita, Hideo ; Kohda, Tomoko ; Fukuoka, Shin Ichi ; Nakamura, Yutaka ; Fukuda, Shinji ; Hase, Kouji ; Ohno, Hiroshi ; Fujinaga, Yukako. / Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity. In: Nature Communications. 2015 ; Vol. 6.
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