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The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption |
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| Authors: | Matsumura Takuhiro Jin Yingji Kabumoto Yuko Takegahara Yuki Oguma Keiji Lencer Wayne I Fujinaga Yukako |
| Institution: | 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.; Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.; GI Cell Biology, Children's Hospital Medical Center, Enders 720, 300 Longwood Ave., Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Enders 720, 300 Longwood Ave., Boston, MA 02115, USA.; The Harvard Digestive Diseases Center, Enders 720, 300 Longwood Ave., Boston, MA 02115, USA. |
| Abstract: | The type B botulinum neurotoxin (BoNT) elicits flaccid paralysis and death in humans by intoxicating peripheral nerves after oral absorption. Here, we examine the function of the haemagglutinin (HA), a non-toxic component of the large 16S BoNT complex. We find that the HA acts in the intestine to disrupt epithelial barrier function by opening intercellular tight and adherens junctions. This allows transport of BoNT and other large solutes into the systemic circulation and explains how the type B BoNT complexes are efficiently absorbed. In vitro , HA appears to act on the epithelial cell via the basolateral membrane only, suggesting the possibility of another step in the absorptive process. These studies show that the 16S BoNT complex is a multifunctional protein assembly equipped with the machinery to efficiently breach the intestinal barrier and act systemically on peripheral nerves. |
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