|Cheng, Luisa Wai Wai|
Submitted to: Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2008
Publication Date: 5/2/2008
Citation: Cheng, L.W., Onisko, B.C., Johnson, E.A., Reader, J.R., Griffey, S.M., Larson, A.E., Tepp, W.H., Stanker, L.H., Brandon, D.L., Carter, J.M. 2008. Effects of purification on the bioavailability of botulinum neurotoxin type A. Toxicology. 249(2008):123-129. Interpretive Summary: Botulinum neurotoxins are extremely toxic proteins produced by the foodborne pathogen Clostridium botulinum and related bacteria. Most toxicity studies have been done using highly purified toxins, but toxins produced in bacterial cultures and found in contaminated foods contain additional nontoxic proteins that appear to stabilize the toxin. It is unknown whether crude preparations of botulinum toxin are more or less toxic than the purified toxin. We fed mice foods spiked with crude and pure toxins, to determine how well the toxins were absorbed. Our results would help scientists understand how the toxin works, and in the development of strategies for maintaining a safe and secure food supply.
Technical Abstract: Botulinum neurotoxins (BoNTs) are some of the most potent biological toxins for humans. They are primarily produced by the gram-positive, anaerobic spore-forming bacterium, Clostridium botulinum. In bacterial cultures, secreted BoNTs are associated with non-toxic accessory proteins such as hemagglutinins that facilitate the formation of large protein complexes. Neurotoxin-associated proteins (NAPs) have been shown to play an important role in the oral toxicity of BoNTs by protecting BoNTs from degradation and digestion by gastric juices. Most toxicity studies using BoNTs have been performed using highly purified toxin. In this study, the toxicities of purified and crude BoNT/A toxin preparations were compared. Protein components secreted into culture supernatants along with BoNT/A were identified by mass spectrometry and the contribution of extraneous proteins found in the soluble crude toxin extracts to the toxicity of BoNTs was determined in a mouse model of botulinum intoxication. Quantitative analysis of crude toxin composition permitted assessment of the impact of accessory proteins on the oral bioavailability of BoNT/A toxin in food matrices.