Botulinum Hemagglutinin: Critical Protein for Adhesion and Absorption of Neurotoxin Complex in Host Intestine

Botulinum hemagglutinin (HA) is one of the auxiliary protein components of the botulinum neurotoxin (BoNT) complex, the most lethal toxin known. HA promotes the intestinal absorption of BoNT by at least two mechanisms, resulting in high oral toxicity. One of the mechanisms is the attachment of large progenitor toxin complexes (L-PTCs) to the cell surface of the intestinal epithelium by the carbohydrate-binding activity of HA. The other is epithelial barrier disruption by the E-cadherin-binding activity of HA. The carbohydrate-binding activity of HA also promotes attachment to the basolateral cell surface, which increases the frequency of contact between HA and E-cadherin. Together, the carbohydrate-binding activity of HA is critical for the intestinal absorption of BoNTs. The trimeric triskelion-shaped structure of HA confers the multivalent binding to its ligands and increases the pathogenic biological activities of HA.