Research Projects: Many bacterial toxins are able to damage the host severely, even at very low concentrations. Most bacterial toxins are enzymes that act catalytically and with high specificity on the 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 machinery of membrane trafficking and the functions of intracellular organelles. Studies that elucidate toxin trafficking could provide valuable information about basic cellular function, aid our understanding of the pathology induced by these toxins, and help in the development of effective therapeutic strategies against them. Our laboratory group is studying the transport mechanisms of the botulinum neurotoxin complex, which must pass through the digestive tract and cross the epithelial barrier lining the intestine to cause food-borne botulism.
Hypothetical model for intestinal absorption of botuliunum neurotoxin complex (type B 16S toxin). We propose a three-step mechanism by which the botulinum neurotoxin complex breaches the intestinal epithelial barrier. (1) Apically located 16S toxin is transcytosed.(2) Once located in the basolateral compartment, HA of the 16S toxin binds to E-cadherin, and thereby disrupts the paracellular barrier. (3) A large amount of toxin accumulates in the basolateral area via paracellular movement.