The many journeys of botulinum neurotoxins and the bacteria that produce them—evolutionary, geographic, and research-related movements that have contributed to our understanding of a diverse pathogen

SUMMARYBotulism is a neuroparalytic intoxication caused by a collection of large proteins, known as botulinum neurotoxins (BoNTs), that are related in amino acid sequence and structure. The extreme potency of BoNTs can be traced to their ability to access and enter cholinergic nerve terminals, their enzymatic nature, and their persistence within these cells. The extreme diversity seen among the BoNTs (7 serotypes and 44 subtypes) and the bacteria that produce them (7 species) stands in stark contrast to its close relative, tetanus toxin, which exists as a single protein entity produced by a single bacterial strain. Botulism may take many forms. It can be due to direct ingestion with BoNT (foodborne), or it may be the consequence of germination and toxin production within the body (infant and adult toxicoinfections, wound botulism). As BoNT-producing organisms are soil inhabitants, the cycle that results in botulism begins when the spores of these bacteria are moved to a location that is favorable for its growth and toxin production, be that in foods, humans, or animals. Multiple researchers in the United States did pioneering work concerning the etiology of botulism, including the identification of different types, the recognition of various host sensitivities, and the necessary conditions for germination and toxin production of these bacteria. As part of their work, several large collections of BoNT-producing bacteria were amassed. This review is a culmination of historical events relating to botulism in the United States and provides listings containing source information on strains from various collections that have provided valuable reference bacteria for basic research studies on botulism and the development of diagnostic tests, quality control testing, and botulism treatments and countermeasures, such as antisera and vaccines.