Clostridium Toxicity

Classical bacterial exotoxins, such as diphtheria toxin, cholera toxin, clostridial neurotoxins, and the anthrax toxins are enzymes that modify their substrates within the cytosol of mammalian cells. To reach the cytosol, these toxins must first bind to different cell-surface receptors and become subsequently internalized by the cells. To this end, many bacterial exotoxins contain two functionally different domains. The binding (B-) domain binds to a cellular receptor and mediates uptake of the enzymatically active (A-) domain into the cytosol, where the A-domain modifies its specific substrate (see Figure 1). Thus, three important properties characterize the mode of action for any AB-type toxin selectivity, specificity, and potency. Because of their selectivity toward certain cell types and their specificity for cellular substrate molecules, most of the individual exotoxins are associated with a distinct disease. Because of their enzymatic nature, placement of very few A-domain molecules in the cytosol will normally cause a cytopathic effect. Therefore, bacterial AB-type exotoxins which include the potent neurotoxins from Clostridium tetani and C. botulinum are the most toxic substances known today. However, the individual AB-type toxins can greatly vary in terms of subunit composition and enzyme activity (see Table 2). 

Toxins from Corynebacterium diphtheriae or Clostridium tetani are water soluble proteins, which effectively constitute the respective vaccine antigens. However, they are treated with formaldehyde to eliminate or reduce the associated toxicity to... 

A thiolase (Eq. 13-35) from Clostridium kluyveri is one of only two known selenoproteins that contain selenomethionine.569 However, the selenomethionine is incorporated randomly in place of methionine. This occurs in all proteins of all organisms to some extent and the toxicity of selenium may result in part from excessive incorporation of selenomethionine into various proteins. 

There were four deaths in previously healthy women due to endometritis and toxic shock syndrome within 1 week after medically induced abortions with oral mifepristone 200 mg and vaginal misoprostol 800 micrograms in two cases Clostridium sordellii was found (19). Another similar case was reported in Canada in 2001. Endometritis and toxic shock syndrome associated with C. sordellii are rare. Of 10 cases identified by authors in the previous literature, eight occurred after the delivery of live-born infants, one after a medical abortion, and one was not associated with pregnancy. The cases produced an FDA alert with a Dear Health Care Provider letter from the manufacturer and publication of a Dispatch in the Morbidity and Mortality Weekly Report (20). 

Fischer M, Bhatnagar J, Guarner J, Reagan S, Hacker JK, Van Meter SH, Poukens V, Whiteman DB, Iton A, Cheung M, Dassey DE, Shieh WJ, Zaki SR. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005 353(22) 2352-60. 

Centers for Disease Control and Prevention. Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol—United States and Canada, 2001-2005. MMWR Morb Mortal Wkl Rep 2005 54 724. 

In April of 2000, a contaminated batch of heroin began a deadly march across Great Britain. By August, more than 40 people in England, Wales, Scotland, and Ireland died. Researchers eventually identified Clostridium vovyi type A, a highly toxic bacterium that grows in soil and animals. Clostridium itself is harmless, but its dormant spores produce deadly toxins when released. 

Antibiotics effectively kill the bacteria, but nothing in modern medicine could combat the toxicity of the Clostridium spores. The Clostridium infection caused massive inflammation of vital organs, internal hemorrhaging, and death. Experts say there is no telling when or where it may strike again. 

O Sullivan G, Mohammed N, Foran P, Lawrence G, Dolly O (1999) Rescue of exocytosis in botulinum toxin A-poisoned chromaffin cells by expression of cleavage-resistant SNAP-25. Identification of the minimal essential C-terminal residues. J Biol Chem 274 36897-904 Oberg SG, Kelly RB (1976) The mechanism of beta-bungarotoxin action. I. modification of transmitter release at the neuromuscular junction. J Neurobiol 7 129 11 Ohishi I, Sugii S, Sakaguchi G (1977) Oral toxicities of Clostridium botulinum toxins in response to molecular size. Infect Immun 16 107-9... 

Botulinum toxin is produced by the bacterium Clostridium botulinum it is the most toxic protein known. The toxin consists of a heavy chain and a light chain the hght chain has protease activity, which degrades a cellular protein (SNAP-25) required for the normal release of neurotransmitters from the axon endings. The consequent lack of release of acetylcholine results in muscle paralysis. 

Botulinum toxin is both a medication and a neurotoxin, produced by the bacterium Clostridium botulinum. It is the most toxic protein known. It can be used to treat muscle spasms, and is sold commercially under various names (Botox, Dysport, Myobloc, etc.). Botox Cosmetic and Vistabel are available for cosmetic treatment. The toxin protein consists... 

Some additives clearly serve an important function. Preservatives help to prevent food from spoiling and enable processed food to be stored for much longer. They reduce the likelihood of bacterial contamination in the food we eat. Sodium nitrite is added to cured meat, for example, to prevent the growth of organisms like Clostridium botulinum, which causes severe toxicity, botulism (see pp. 249-51). Preservatives also reduce chemical degradation and so allow food to have a longer shelf life. Other additives may also have a beneficial function, for example artificial sweeteners reduce the sugar intake of people who suffer from diabetes or obesity. 

Coleman, I. (1954). Studies on the oral toxicity of Clostridium botulinum toxin, type A. Can J. Biochem. Physiol. 32 27-34. 

Morton, H. (1961). The toxicity of Clostridium botulinum type A toxin for various species of animals, including man. Armed Services Technical Information Agency. ICR Contract Report 1-29. 

Ohishi, I. (1984). Oral toxicities of Clostridium botulinum type A and B toxins from different strains. Infect. Immun. 43 487-90. 

Sakaguchi, G., Sakaguchi, S. (1974). Oral toxicities of Clostridium botulinum type E toxins of different forms. Jpn. J. Med. Sci. Biol. 27 241. ... 

Bohnel, H., Schwagerick, B., Gessler, F. (2001). Visceral botulism-a new form of bovine Clostridium botulinum toxication. J. Vet. Med. A Physiol. Pathol. Clin. Med. 48 373-83. 

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