Botulinum neurotoxins human intoxication

The botulinum neurotoxins (BoNTs) comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium Clostridium botulinum and in rare cases by Clostridium baratii and Clostridium butyricum (Habermann and Dreyer, 1986 Harvey et ah, 2002 Simpson, 2004). These toxins act on peripheral cholinergic synapses to inhibit spontaneous and impulse-dependent release of acetylcholine (ACh) (Brooks, 1956 Kao et al., 1976). Intoxication by BoNT results in muscle weakness, which can be fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation (Dickson and Shevky, 1923). The BoNTs are the most potent substances in nature, and exposure to as httle as 1-3 ng/kg may be sufficient to cause human lethahty (GUI, 1982 Middlebrook and Franz, 1997 Amon et al., 2001). 

Since botulinum is a neurotoxin, large-scale production should meet biosafety level 3 containment and strict handling to avoid the possible human intoxication. Fermentation is carried out in complex medium containing casein hydrolysate, yeast extract, and glucose for 4 days. Then, botulinum toxin is precipitated with 3 N sulfuric acid followed by purification with DEAE-Sephadex column. Botulinum toxin was crystallized then and purified by additional steps using various affinity and size exclusion chromatography. Purity and quality were checked by animal testing. Production and purification steps vary with Clostridium strain used and botulinum type to be produced. ... 

The toxin BoTx, produced by the anaerobe Clostridium botulinum, has the reputation of being the most toxic substance by weight known to humans, being at least 5000 times more toxic than sarin. Botulism is a disease of both humans and animals. Seven dilferent functionally related neurotoxins are produced by various strains (A-G). Botulism is essentially an intoxication, brought on by ingestion of the toxin produced by clostridial infection of food, usually incorrectly canned meats. Primary botulism, a direct infection, is rare and only affects infants in the human species. Botulinum intoxication can, however, be treated, and this modifies the toxicity considerably. It is estimated that less than 10 % of natural cases receiving ventilatory and antitoxin support are fatal. 

---