Botulinum Toxin Complex Serotype B-Okra Exerts Systemic Toxicity via the Oral Route by Disrupting the Intestinal...

Area of Science:

• Microbiology
• Toxicology
• Gastroenterology

Background:

• Botulinum neurotoxins (BoNTs) are potent toxins associated with neurotoxin-associated proteins, forming progenitor complexes.
• Different complexes exhibit varying oral toxicity and target specific intestinal cells.
• Hemagglutinin (HA) is a key protein facilitating BoNT intestinal absorption and possessing barrier-disrupting activities.

Purpose of the Study:

• To investigate the role of the B-Okra toxin complex (L-PTC/B-Okra) in oral toxicity.
• To determine if the barrier-disrupting activity of L-PTC/B-Okra contributes to its toxicity.

Main Methods:

• Established an in vitro system for reconstituting and purifying recombinant L-PTC/B-Okra.
• Created a mutant recombinant L-PTC/B-Okra (rL-PTC/B-KA) lacking barrier-disrupting activity but retaining carbohydrate-binding function.
• Assessed the oral toxicity of the wild-type and mutant complexes.

Main Results:

• Recombinant L-PTC/B-Okra was successfully reconstituted and purified.
• The mutant rL-PTC/B-KA exhibited significantly reduced oral toxicity compared to the wild-type.
• The B-Okra toxin's barrier-disrupting activity was identified as crucial for its oral toxicity.

Conclusions:

• The B-Okra toxin complex disrupts the epithelial barrier of enterocytes.
• This disruption is the primary mechanism underlying its oral toxicity.
• Targeting the barrier-disrupting activity could be a strategy to mitigate BoNT oral toxicity.