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

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  • Takuhiro Matsumura

    (Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamada-oka, Suita, Osaka 565-0871, Japan)

  • Yo Sugawara

    (Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamada-oka, Suita, Osaka 565-0871, Japan)

  • Masahiro Yutani

    (Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamada-oka, Suita, Osaka 565-0871, Japan)

  • Sho Amatsu

    (Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamada-oka, Suita, Osaka 565-0871, Japan)

  • Hideo Yagita

    (Juntendo University School of Medicine, 2-1-1 Hongo, Tokyo 113-8421, Japan)

  • Tomoko Kohda

    (School of Life and Environmental Science, Osaka Prefecture University, 1-58, Rinku-oraikita, Izumisano, Osaka 598-8531, Japan)

  • Shin-Ichi Fukuoka

    (School of Culture and Creative Studies, Aoyama Gakuin University)

  • Yutaka Nakamura

    (Faculty of Pharmacy, Keio University)

  • Shinji Fukuda

    (Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medial Sciences (IMS))

  • Koji Hase

    (Faculty of Pharmacy, Keio University)

  • Hiroshi Ohno

    (Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medial Sciences (IMS)
    Graduate School of Medical Life Science, Yokohama City University
    Graduate School of Medicine, Chiba University)

  • Yukako Fujinaga

    (Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamada-oka, Suita, Osaka 565-0871, Japan)

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.

Suggested Citation

  • Takuhiro Matsumura & Yo Sugawara & Masahiro Yutani & Sho Amatsu & Hideo Yagita & Tomoko Kohda & Shin-Ichi Fukuoka & Yutaka Nakamura & Shinji Fukuda & Koji Hase & Hiroshi Ohno & Yukako Fujinaga, 2015. "Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7255
    DOI: 10.1038/ncomms7255
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