Biosciences Research Seminar - Employing protein receptors as innovative capture structures for the detection of highly potent clostridial protein toxins

Botulinum neurotoxins (BoNTs) are the most potent toxins known and the causative agents of botulism in both humans and animals. Diagnostics is complicated by their extraordinary potency and the existence of seven established, clinically relevant serotypes with more than 40 variants (subtypes), as all pathogenic variants have to be detected reliably. Monoclonal antibodies, which are usually employed for enrichment of BoNTs from complex matrices, potentially fail to detect selected subtypes due to escape mutations at the mAbs’ binding epitopes. Since only toxins exhibiting high affinity receptor binding are able to mediate high toxicity in vivo, integrating cellular receptors in detection assays instead of antibodies for toxin enrichment represents a novel approach. Here I describe how we deciphered toxin receptor interaction on the molecular level and employed high-affinity receptor interactions in a bi-functional assay for detection of BoNT serotypes A and B. Subsequently, the approach was successfully expanded to detect C. perfringens enterotoxin (CPE) responsible for the second most cases of bacterial food-borne illnesses and antibiotic-associated diarrhea by a rapid detection system.