Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/16/2013
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: Botulinum neurotoxins(BoNTs)secreted by Clostridium botulinum are some of the most poisonous toxins in nature and considered to be major bioterrorism threats. To date, seven BoNT subtypes (A to G) have been identified. When secreted from bacteria, some BoNTs associate with a non-toxic, non hemagglutinin protein and hemagglutinins(neurotoxin associated proteins or NAPs)forming large complexes. NAPs have previously been shown to shield BoNT from the low pH and digestive environment of the gastrointestinal tract and promote holotoxin crossing of the intestinal epithelia. Ingested BoNTs must cross the intestinal cell barriers before reaching the blood circulation and on to their target peripheral cholinergic neurons. It is still unclear how these large BoNT complexes traverse the intestinal epithelial barriers and whether they remain as large complexes while they do so. Here, we monitored the transit of BoNT holotoxins and NAPs in vivo and through Caco2 cells over time. When Caco2 cells were exposed to either BoNT/A or BoNT/B complexes, BoNT was detected inside cells beginning at two hours. Holotoxin transit was slower beginning at four hours indicating that although toxin alone is sufficient for entry, the presence of NAPs enhanced the rate of entry. Understanding the uptake of these toxin complexes will aid in the development of new measures designed to prevent oral intoxication.