A Novel Botulinum Neurotoxin, Previously Reported as Serotype H, Has a Hybrid-Like Structure With Regions of Similarity to the Structures of Serotypes A and F and Is Neutralized With Serotype A Antitoxin

Abstract

Botulism is a potentially fatal paralytic disease caused by the action of botulinum neurotoxin (BoNT) on nerve cells. There are 7 known serotypes (A-G) of BoNT and up to 40 genetic variants. Clostridium botulinum strain IBCA10-7060 was recently reported to produce BoNT serotype B (BoNT/B) and a novel BoNT, designated as BoNT/H. The BoNT gene (bont) sequence of BoNT/H was compared to known bont sequences. Genetic analysis suggested that BoNT/H has a hybrid-like structure containing regions of similarity to the structures of BoNT/A1 and BoNT/F5. This novel BoNT was serologically characterized by the mouse neutralization assay and a neuronal cell-based assay. The toxic effects of this hybrid-like BoNT were completely eliminated by existing serotype A antitoxins, including those contained in multivalent therapeutic antitoxin products that are the mainstay of human botulism treatment.

Bacterial Signaling to the Nervous System through Toxins and Metabolites

“…BoNTs are a genetically diverse group that can be classified into seven serotypes (BoNT/A – BoNT/G) based on immunoreactivity. An additional serotype (BoNT/H) was proposed but recent studies suggest it is a hybrid of BoNT serotypes A and F [11]. …”

Impact of Clostridium botulinum genomic diversity on food safety

“…Hybrids of type C and type D neurotoxin (type C/D or type D/C) are formed more frequently than type C or type D neurotoxin [30]. A highly novel neurotoxin (type FA (Figure 1), also known as type H and type HA) that contains regions of similarity to type A neurotoxin and type F neurotoxin has been recently identified and is being characterised [31, 32, 33, 34, 35, 36]. Hybrid neurotoxin subtypes have been identified, e.g.…”

Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup—Allergic Reactions to Botulinum Antitoxin: A Systematic Review

“…Thus, serum antibody raised for antitoxin against one serotype does not cross-react with other serotypes [5]. Recently, reports of new toxin types have been published, including a novel toxin subsequently shown to be hybrid type A/F fully neutralized by heptavalent botulinum antitoxin (HBAT) [6,7], and a novel toxin identified and assembled from the published gene sequence of a C. botulinum isolate [8].…”