Characterization of Clostridium botulinum Type B Neurotoxin Associated with Infant Botulism in Japan release_h2gupxpm6jblnffxfmk7u5nie4

Abstract

The neurotoxin of strain 111 (111/NT) associated with type B infant botulism showed antigenic and biological properties different from that (Okra/NT) produced by a food-borne botulism-related strain, Okra. The specific toxicity of 111/NT was found to be about 10 times lower than that of Okra/NT. The monoclonal antibodies recognizing the light chain cross-reacted with both neurotoxins, whereas most of the antibodies recognizing the carboxyl-terminal half of the heavy chain of Okra/NT did not react to 111/NT. Binding experiments with rat brain synaptosomes revealed that <jats:sup>125</jats:sup>I-labeled 111/NT bound to a single binding site with a dissociation constant (<jats:italic>K<jats:sub>d</jats:sub> </jats:italic>) of 2.5 nM; the value was rather lower than that (0.42 nM) of <jats:sup>125</jats:sup>I-Okra/NT for the high-affinity binding site. In the lipid vesicles reconstituted with ganglioside GT1b, <jats:sup>125</jats:sup>I-Okra/NT interacted with the amino-terminal domain of synaptotagmin 1 (Stg1N) or synaptotagmin 2 (Stg2N), fused with the maltose-binding protein, in the same manner as the respective full-length synaptotagmins, and the <jats:italic>K<jats:sub>d</jats:sub> </jats:italic> values accorded with those of the low- and high-affinity binding sites in synaptosomes. However, <jats:sup>125</jats:sup>I-111/NT only exhibited a low capacity for binding to the lipid vesicles containing Stg2N, but not Stg1N, in the presence of ganglioside GT1b. Moreover, synaptobrevin-2, an intracellular target protein, was digested to the same extent by the light chains of both neurotoxins in a concentration-dependent manner. These findings indicate that the 111/NT molecule possesses the receptor-recognition site structurally different from Okra/NT, probably causing a decreased specific toxicity.
In application/xml+jats format

Archived Files and Locations