[Clostridium botulinum and botulinum neurotoxin]

Brain Nerve. 2011 Jul;63(7):755-61.
[Article in Japanese]

Abstract

Clostridium botulinum is a gram-positive anaerobic rod that forms endospores. This bacterium produces large molecular toxin complexes, namely botulinum toxin complexes (progenitor toxins). It (L toxin complex) is composed of a single neurotoxin molecule (BoNT with a molecular weight of 150 kDa), a single nontoxic nonhemagglutinin molecule (NTNHA), and a hemagglutinin complex (HA). On food-borne botulism, nontoxic components have the roles of protecting toxin protein from the degeneration and degradation action of acids and proteases existing in the gastrointestinal tract. The HA facilitates transport when progenitor toxins cross the intestinal epithelial barrier to enter the systemic circulation. BoNT disassociates from the toxin complexes in the systemic circulation. BoNT is immunologically classified into 7 serotypes, A to G. Serotypes A, B, E, and F are the causative agents of human botulism. The active BoNT molecules are composed of 2 chains that are termed the heavy chain (c. 100 kDa) and the light chain (c. 50 kDa); these are covalently connected by a disulfide bond. The light chains have a tetrahedral zinc binding motif conteining a consensus HExxH amino acid sequence, and exhibit metalloprotease activity. After BoNTs reach the neuromuscular junction (the peripheral nerve ending), these are endocytosed in lipid vesicles (synaptic vesicles), and the light chain is released into the cytosol of a nerve cell via a translocation event through the phospholipid vesicle membrane. The light chains of BoNTs (zinc endopeptidases) cleave core proteins involved in the trafficking and release of neurotransmitters (acetylcholine), including synaptobrevin, SNAP-25, and syntaxin. These proteins comprise the synaptic members of the SNARE complex (soluble NSF (N-ethylmaleimide-sensitive fusionprotein) attachment protein) that have a central role in membrane fusion events. The selective proteolysis of these SNARE proteins inhibits neurotransmitter release from neurons. Botulism occurs via a series of processes that cause muscular paralysis in human and animals.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Animals
  • Botulinum Toxins* / pharmacology
  • Clostridium botulinum / metabolism*
  • Humans
  • Neuromuscular Junction / drug effects

Substances

  • Botulinum Toxins