Botulinum neurotoxins lethality

The role of C2 toxin in disease is not clear because all C. botulinum strains that produce C2 toxin also synthesize extremely potent neurotoxins, the effector molecules of botulism. When Simpson compared the pharmacological properties of C. botulinum neurotoxin type Cl with C2 toxin in detail, it became obvious that C2 toxin does not cause the flaccid paralysis symptoms attributed to classic botulism. However, isolated C2 toxin is a potent enterotoxin that proves lethal in various animals 2 pmol of C2 toxin readily kill mice, rats, guinea pigs, and chickens within 1 h after application. For mice, the LD50 (i.v.) of C2 toxin is less than 50 ftnol. Ohishi and Odagiri also reported that C2 toxin causes necrotic, hemorrhagic lesions in the intestinal wall, whereas Simpson reported that C2 toxin elicits hypotension as well as fluid accumulation in the lungs. ... 

Clostridium botulinum neurotoxin, the most effective toxin known to date, with a mice lethal dose of about 50 pg/mL (330 fmol/mL) was the target antigen in IPCR assays developed by Wu et al. [48] and Chao et al. [88]. In these assays, detection limits of 5 fg (33 amol) and 50 fg (330 amol), respectively, were found. 

Adler, M., Dinterman, R., and Wannemacher, R.W., Protection by the heavy metal chelator N, N, N, N -tetrakis(2-pyridyknethyl)ethylediamine (TPEN) against the lethal action of botulinum neurotoxin A and B, Toxicon, 35, 1089, 1997. 

The seven serotypes of botulinum toxin produced by Clostridium botulinum are the most toxic substances known. They are associated with lethal food poisoning after the consumption of canned foods. This family of toxins was evaluated by the United States as a potential biological weapon in the 1960s and is believed to be an agent that could be used against our troops. Unlike other threat toxins, botulinum neurotoxin appears to cause the same disease after inhalation, oral ingestion, or injection. Death results from skeletal muscle paralysis and resultant ventilatory failure. Because of its extreme toxicity, the toxin typically cannot be identified in body fluids, other than nasal... 

Until recently, there have been only two primary techniques available for the detection of botulinum neurotoxins. The first of these, which is the most widely accepted and sensitive technique for the detection of botulinum neurotoxins in semm and food extracts, is the mouse bioassay (Sakaguchi, 1983). Although the mouse bioassay is the most sensitive method, with the ability to detect less than 5 mouse 50% lethal doses (MLD5os)/mL, the assay takes up to four days to complete and requires a large number of mice if the toxin is to be quantified. In addition, the mouse toxicity results are not in themselves specific specificity is imparted only by carrying out parallel toxin neutralization tests with homologous antisera (Shone et al., 1985). Furthermore, as future modifications are made to botulinum neurotoxins relative to their use as therapeutic agents, quantification relative to its toxicity to mice may not be possible. Thus, despite the apparent sensitivity offered by the mouse bioassay, its use as a routine detection technique for botulinum neurotoxins is not only impractical, but also may be obsolete in some areas of research. 

Eotuhnum neurotoxins (EoNTs) are perhaps the most lethal toxins known. EoNTs are a set of seven serotypes (A, E, C, D, E, F and G) that are produced almost exclusively by the bacteria Clostridium botulinum. Serotypes C and D are found in birds and non-human mammals. Types A, E, E and F have been implicated in human cases of botuhsm. LD50 values for EoNTs range from 1.1 to 2.5 ng/kg body weight [7]. EoNTs have been associated with a variety of foods, including honey, chili, and hash browns. Isolation of toxins from the suspected food is the current means of diagnosis. 

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