Submitted to: Toxicon
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2011
Publication Date: 5/11/2011
Citation: Cheng, L.W., Henderson II, T.D. 2011. Comparison of oral toxicological properties of botulinum neurotoxin. Toxicon. 58:62-67. Interpretive Summary: Botulinum neurotoxins (BoNTs) are some of the most potent toxins to humans. These toxins are likely targets for use in intentional adulteration of food or animal feeds and are thus classified as Select Agents. BoNT types A, B and E cause most of the foodborne illnesses. However, little is known about the effects of food on the absorption of these toxins. In this study, we used mouse models of botulism to compare potencies of BoNT/A and B, two of the most common botulinum toxins involved in foodborne contaminations in humans. We demonstrated that several factors, such as the presence of other proteins, the size of the toxin when associated with other proteins, or the type of food present, could either enhance or reduce the toxic impact of BoNTs. Our results would further understanding of the biology of toxins in an animal and would be invaluable in advancing food safety and protection.
Technical Abstract: Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments.