Oral toxicities of Clostridium botulinum toxins in response to molecular size

Abstract

Clostridium botulinum type A, B, and F toxins of different molecular sizes were fed to mice to compare the oral toxicities. The progenitor toxin, a complex of a toxic and nontoxic component, of any type was higher in oral toxicity to mice than the dissociated toxic component or the derivative toxin. The former may no doubt play a more important role in the pathogenesis of food-borne botulism. The higher oral toxicity possessed by the progenitor toxin, including the exceptionally high one found with type B-L toxin, can be explained solely by the protection afforded by the nontoxic component attached to the toxic component. The possibility of the highest oral toxicity of type B-L toxin to humans is discussed.

HA-33 facilitates transport of the serotype D botulinum toxin across a rat intestinal epithelial cell monolayer

“…Because the large TCs exhibit significantly higher oral toxicity than pure BoNT, the auxiliary nontoxic proteins have been considered essential for food poisoning (Sakaguchi et al, 1984). Although their most accepted function is as a safeguard against the harsh conditions in the digestive tract (Halliwell, 1954;Ohishi et al, 1977;Sugii et al, 1977a, b;Bonventre, 1979;Ohishi & Sakaguchi, 1980;Ohishi, 1984;Chen et al, 1998;Niwa et al, 2007), the role of the nontoxic proteins is still under debate. There is some evidence that the HA components of auxiliary nontoxic proteins play a role in absorption across the intestinal epithelium (Fujinaga et al, 1997(Fujinaga et al, , 2004Nishikawa et al, 2004;Uotsu et al, 2006;Niwa et al, 2007Niwa et al, , 2010.…”

“…The TCs (M-TC, L-TC and LL-TC) display greater oral toxicity than pure BoNT (Ohishi et al, 1977;Sakaguchi et al, 1984). Pure BoNT without auxiliary nontoxic components is susceptible to the proteolytic and acidic conditions in the digestive tract (Halliwell, 1954;Ohishi et al, 1977;Sugii et al, 1977a, b;Bonventre, 1979;Ohishi & Sakaguchi, 1980;Ohishi, 1984;Chen et al, 1998;Niwa et al, 2007), indicating that the nontoxic components serve to protect BoNT against the conditions of the gastrointestinal tract. There is evidence that the L-TC transports across the intestinal epithelial cell monolayer more effectively than pure BoNT (Fujinaga et al, 1997(Fujinaga et al, , 2004Niwa et al, 2007, 2010; Inui et al, 2010).…”

Botulogenic Properties of Vegetables With Special Reference to the Molecular Size of the Toxin in Them

“…The dissociated 7 s toxic component is so labile that it may not function as an oral toxin Ohishi et al 1977). With regard t o type A and B toxins, the larger the molecular size the higher the oral toxicity to mice .…”

Characterization of Nontoxic‐Nonhemagglutinin Component of the Two Types of Progenitor Toxin (M and L) Produced by Clostridium botulinum Type D CB‐16

“…The L and LL toxins show hemagglutinating activity, but the M toxin does not (24). It has been proposed that the L toxin is formed by non-covalent binding with HA components to the M toxin which is composed of NTNH and neurotoxin (23). Although the NTNH and HA have been implicat-ed in the protection of the botulinum neurotoxin against degradation by gastric juice at a low pH (23,24), their biological functions have not been well defined yet.…”

“…It has been proposed that the L toxin is formed by non-covalent binding with HA components to the M toxin which is composed of NTNH and neurotoxin (23). Although the NTNH and HA have been implicat-ed in the protection of the botulinum neurotoxin against degradation by gastric juice at a low pH (23,24), their biological functions have not been well defined yet. Therefore, it is valuable to examine M and L (LL) toxins in detail by cloning and nucleotide sequencing of the region containing nontoxic component genes.…”