|Cheng, Luisa Wai Wai|
|LAM, TINA - Gilead Sciences Inc|
|MARTCHENKO, MIKHAIL - Keck Graduate Institute|
Submitted to: Meeting Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 10/14/2016
Publication Date: 12/25/2016
Citation: Cheng, L.W., Tam, C.C., Lam, T.A., Stanker, L.H., Martchenko, M. 2016. Identification of botulinum neurotoxin serotype a inhibitors using in vitro cell and oral models of intoxication. TOXINS 2017 Basic Science and Clinical Aspects of Botulinum and Other Neurotoxins. Meeting Proceedings. Toxicon. Rose Puleo ed. 123 supplement:S16-S17 (25 December 2016).
Technical Abstract: Introduction and Objective: Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. There are no treatment options available for treatment except for antitoxin antibody treatment after disease diagnosis and long-term supportive care and hospitalization. Previous work from our laboratory showed that an in vitro Caco2 cell model could simulate uptake profiles of oral intoxication using the mouse as the model. Methods: We used both the in vitro and mouse oral intoxication models to test various chemical compounds and probiotic microorganisms for inhibition of BoNT/A epithelial cell internalization and oral toxicity. Results: We identified biothionol and other drugs as inhibitors of oral BoNT/A intoxication, and using the in vitro cell model, identified several probiotic microorganisms (Saccharomyces boulardii, Lactobacillus acidophilus, Lactobacillus rhamnosus LGG, and Lactobacillus reuteri) that blocked BoNT/A uptake in a dose-dependent manner, while a nonprobiotic strain of Escherichia coli did not prevent toxin internalization. We also showed that inhibition of BoNT/A uptake was not due to the degradation of BoNT/A nor sequestration of toxin via binding to probiotics. Conclusions: These results show that both in vitro and oral models can help identify potential chemical and probiotic treatments that can inhibit BoNT/A intoxication. Therefore, studies to elucidate the initial entry and internalization process of the toxin in the gut are of critical importance because of the potential for development of new therapies to proactively block intoxication or to ameliorate the function of the toxin after ingestion.