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.

We report here the isolation of Clostridium botulinum type C from the medial muscles of the thigh of a gestating gilt with a claw wound and without evidence of septicemia. The pig died with paralytic signs, consistent with wound botulism, similar to episodes in humans.

Botulism is a foodborne, life-threatening neuroparalytic disease caused by Clostridium botulinum, an anaerobic, gram-positive, spore-forming bacteria. Its incidence is unknown and underestimated due to missed diagnoses, especially in remote areas. It is divided into four main clinical types: Infant, adult-onset foodborne, iatrogenic, and wound botulism. The overall goal of the article is to focus on the geographic differences in incidence, including its propensity to high-altitude areas, and shed light on the theories behind this propensity. Infantile botulism is caused by Clostridium botulinum, an anaerobic, spore-forming, gram-positive bacillus. This bacterium is found in soil, water, and air, with a lethal toxin dosage as low as 1 mcg/kg. Botulism can develop through 5 distinct mechanisms, though this article focuses on infantile botulism. Foodborne botulism occurs when a person ingests the preformed toxin. Infantile botulism results from C. botulinum colonization in the gastrointestinal tract of infants younger than 1 year. Wound botulism arises when infected wounds harbor C. botulinum and produce toxin. Iatrogenic botulism is associated with systemic intoxication following cosmetic or therapeutic use of botulinum toxin. Intestinal colonization in individuals older than 1 year leads to toxin production within the gastrointestinal tract, similar to infantile botulism but occurring in older children or adults. Despite these different routes of infection, only 3 primary C. botulinum serotypes account for cases in humans. Type A is most prevalent west of the Mississippi River. Type B is more common in the eastern United States. Type E is frequently found in the Pacific Northwest, particularly in Alaska. Approximately 100 cases of infantile botulism are reported annually in the United States. Around 20% are linked to raw honey consumption, with most cases occurring in infants from immigrant families. In the majority of affected infants, the source of C. botulinum spores remains unidentified. Experts suggest that contamination may result from exposure to environmental sources, such as dust from construction sites or soil.

Botulinum neurotoxins are synthetized by anaerobic, spore-forming bacteria that inhibit acetylcholine release at the level of the neuromuscular and autonomic cholinergic junctions, thus inducing a series of symptoms, the most relevant of which is flaccid paralysis. At least seven serotypes and over 40 subtypes are known, and they are among the most poisonous natural substances. There are different forms of botulism according to the route of contamination, but the clinical manifestation of descending symmetric flaccid paralysis is consistent, regardless of the route of contamination. It is very severe and potentially lethal. The induced paralysis lasts as long as the toxin is active, with variable length, according to the serotype of the toxin. This transient activity, as well as the precise mechanism of action, are the basis for the rationale behind use of the toxin in therapy for several clinical conditions, particularly, spastic conditions, as well as chronic migraine and axillary hyperhidrosis. The toxin has also been approved for the reduction in facial wrinkles; all these clinical applications, coupled with the toxin's risks, have earned botulinum the title of a two-faced Janus protein. No approved vaccines are currently available, andthe only approved antidotes are the human specific intravenous immunoglobulins for infant botulism and the heptavalent equine immunoglobulins/(F(ab')2 for adults. Nanobodies, which show great promise, may penetrate neuronal cells to inactivate the toxin within the cytoplasm, and Ebselen, a non-toxic, economic, small-molecule inhibitor, has the characteristic of inhibiting the toxin irrespective of the serotype. Botulism is a rare but potentially fatal syndrome of diffuse, flaccid paralysis caused by botulinum neurotoxin (BoNT), a neurotoxin elaborated by the bacterium Clostridium botulinum and 6 other clostridial genospecies. Several other etiologies of botulism have been described since its recognition as a foodborne entity in Germany and Belgium in the 1800s, including wound botulism, iatrogenic botulism, and inhalational botulism. The administration of polyvalent antitoxin to BoNT mitigates the clinical course of botulism. However, no true antidote exists, and disease management relies on potentially weeks of mechanical ventilation and other resource-heavy therapies while the body's neuromuscular signaling mechanisms recover. BoNT, the most potent poison known to man, is relatively simple to produce, store, and disperse. Thus, this toxin is a subject of intense interest for defense organizations worldwide. Due to its toxicity, BoNT has been previously implicated in biological warfare and bioterrorism plans with state-based actors and terror groups such as the Red Army Faction and Aum Shinrikyo in the 1980s and 1990s. Despite this, BoNT can be managed in accredited biosafety level 2 containment facilities as it is not transmissible following initial exposure.