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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Foodborne Toxin Detection and Prevention Research » Research » Publications at this Location » Publication #304536
Title: Translocation of botulinum neurotoxin serotype a and associated proteins across the intestinal epithelia

Author
item Lam, Tina
item Stanker, Larry
item LEE, KWANGKOOK - University Of California
item JIN, RONGSHENG - University Of California
item Cheng, Luisa

Submitted to: Cellular Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2015
Publication Date: 2/15/2015
Publication URL: https://handle.nal.usda.gov/10113/61262
Citation: Lam, T.I., Stanker, L.H., Lee, K., Jin, R., Cheng, L.W. 2015. Translocation of botulinum neurotoxin serotype a and associated proteins across the intestinal epithelia. Cellular Microbiology. 17(8):1133-1143. doi:10.1111/cmi.12424.

Interpretive Summary: Botulinum neurotoxins (BoNT) are some of the most potent biological toxins. They form large protein complexes that must cross the intestinal barriers to reach the bloodstream. We studied how such large toxins cross the intestinal barriers by evaluating the crossing of the BoNT toxin complex in an oral mouse and in cultured cell models. Understanding the mechanism of how these large toxin complexes cross intestinal barriers will advance our understanding of botulinum toxins and how to design effective therapeutic strategies.

Technical Abstract: Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins and considered to be a major venue of bioterrorist threat. BoNTs associate with neurotoxin associated proteins (NAPs), forming large complexes. NAPs have been shown to shield the BoNT holotoxin from the harsh environment of the gastrointestinal tract and promote its crossing through the intestinal epithelium barrier. It is still unclear whether BoNTs and their NAPs remain as a complex while they traverse the epithelial barrier. In this study, we monitored the transit of BoNT serotype A holotoxin, complex and purified NAPs in cultured and polarized Caco-2 cells, and in the oral mouse model of intoxication over time. BoNT/A and NAPs in complex were detected inside intestinal cells beginning at 2 h post-intoxication. Translocation of BoNT/A holotoxin alone was slower, with detection starting at 4-6 h, indicating that while the holotoxin alone is sufficient for entry, the presence of NAPs enhances the rate of entry. NAPs alone also can be internalized. BoNT/A detection peaks at approximately 6 and 8 h for complex and holotoxin, respectively, and begins to disperse with some remaining in the epithelia after 24 hours. Following translocation in to the intestinal epithelium, BoNT holotoxin and NAPs were observed independent of each other and co-localized. NAPs remain in the intestinal epithelia far longer than BoNT/A holotoxin. Understanding the intestinal uptake of BoNT complexes will aid in the development of new measures designed to prevent or treat oral intoxications.