Many bacterial toxins are able to severely damage the host, even at very low concentrations. Most are enzymes that act catalytically and with high specificity on functional host cell molecules, thereby markedly modulating host homeostasis. The toxins are also often highly efficient in accessing their target molecule in the host. The ingenious transport systems involved often exploit the fundamental membrane trafficking and the functions of intracellular organelles. Therefore, studies seeking to elucidate toxin trafficking could provide us with valuable information about basic cellular function, as well as aiding our understanding of the pathology induced by these toxins and helping us to develop effective therapeutic strategies against them. We are currently engaged in studying the transport mechanisms of the botulinum neurotoxin complex, which must pass down the digestive tract and cross the epithelial barrier lining the intestine to cause food-borne botulism.
Figure
(a) Schematic depiction of the botulinum neurotoxin complex (16S and 12S toxins). Orally ingested neurotoxin complexes cross the intestinal epithelial barrier to cause food-borne botulism.
(b) 16S toxin (green) penetrates the intestinal epithelium.
(c) Interaction of botulinum neurotoxin complexes with the intestinal epithelial barrier. The HA of the botulinum neurotoxin complex binds E-cadherin and disrupts E-cadherin-mediated cell-to-cell adhesion, thereby disrupting the epithelial paracellular barrier.