Interaction of Botulinum Toxin with the Epithelial Barrier

Abstract

Botulinum neurotoxin (BoNT) is a protein toxin (~150 kDa), which possesses a metalloprotease activity. Food-borne botulism is manifested when BoNT is absorbed from the digestive tract to the blood stream and enters the peripheral nerves, where the toxin cleaves core proteins of the neuroexocytosis apparatus and elicits the inhibition of neurotransmitter release. The initial obstacle to orally ingested BoNT entering the body is the epithelial barrier of the digestive tract. Recent cell biology and molecular biology studies are beginning to elucidate the mechanism by which this large protein toxin crosses the epithelial barrier. In this review, we provide an overview of the structural features of botulinum toxins (BoNT and BoNT complex) and the interaction of these toxins with the epithelial barrier.

Oral Application of Charcoal and Humic acids to Dairy Cows Influences Clostridium botulinum Blood Serum Antibody Level and Glyphosate Excretion in Urine

“…Antibody reduction was constant from week 4 to 24; however, four weeks after finishing supplementation (week 26), CD antibodies increased. Figure 2: Dynamics of C. botulinum ABE antibodies in blood serum in relation to the daily application of 400 g charcoal (weeks 1-4), 200 g CC (weeks 5-10), 200 g CC+500 ml sauerkraut juice (SJ) (weeks [11][12][13][14], 120 g humic acid (HA) (weeks 15-18), 200 g CC +100 mL Aquahumin(AH) (weeks [19][20], 100 g CC +50 mL Aquahumin(AH) (weeks [21][22], and without supplementation (weeks [23][24][25][26]. There was a significant reduction of antibody levels with a daily supplementation of charcoal or humic acids beginning from week 6 (P<0.01 for week 6, P<0.001 for weeks 8-24, and P<0.05 for week 26.…”

“…There was a significant reduction of antibody levels with a daily supplementation of charcoal or humic acids beginning from week 6 (P<0.01 for week 6, P<0.001 for weeks 8-24, and P<0.05 for week 26. [11][12][13][14], 120 g humic acid (HA) (weeks 15-18), 200 g CCl +100 mL Aquahumin(AH) (weeks [19][20], 100g CC +50 mL AH (weeks [21][22] and without supplementation (weeks 23-26) on the dynamic of C. botulinum CD antibodies in blood serum. There was a significant reduction in antibody levels from daily supplementation with charcoal and humicacids (P<0.01 and P<0.001) for weeks 14-24.…”

“…The whole toxin complex seems to be absorbed from the intestine into the lymphatics in the rat ligated duodenum loop assay. Molecular dissociation occurs immediately after BoNT complexes, designated progenitor toxins, are absorbed into the lymphatics [20]. Botulinum progenitor toxins are found in three forms with molecular masses of 900 kDa (LL toxin for type A), 500 kDa (L toxin for types A, B, C, D and G) and 300 kDa (M toxin for types A, B, C, D, E and F).…”

Complexity of Botulinum Neurotoxins: Challenges for Detection Technology

“…After oral uptake into the body, BoNT molecules are protected from the harsh conditions in the gastrointestinal tract by NTNHA which shields the toxin in a pH-dependent manner . Within the small intestine, BoNT complexes bind to microvilli mediated by the hemagglutinins (Fujinaga 2006(Fujinaga , 2010. The mechanism by which the BoNT complex crosses the epithelial barrier is still under debate.…”

“…The mechanism by which the BoNT complex crosses the epithelial barrier is still under debate. Two mechanisms have been suggested: receptor-mediated endocytosis with subsequent transcytosis and ternary HA complex mediated destruction of the intercellular junctions, followed by paracellular influx (Maksymowych and Simpson 1998Simpson , 2004Fujinaga et al 2009;Fujinaga 2010), (Fujinaga et al 2012). Directly after absorption of the BoNT complex, it dissociates before it reaches the blood circulation that takes it to its neuronal target cells (Sakaguchi 1982).…”