Gram positive toxins
We’ve covered several Gram positive bugs, who’s primary mechanism of pathogenesis is the production of toxins. Although ability to initiate infection and survive in the human body are significant events in the process of disease, what differentiates several of these organisms is that growth of the bacterium in the human body is not a very important event in contrast to the presence of the exotoxin. For instance, in the case of staphylococcal food poisoning, pathogenesis occurs in the absence of viable bacteria. Improperly prepared food can permit the growth of Staphylococcus aureus, resulting in enterotoxin production and accumulation during bacterial growth outside of the human body. When the food is eaten, even following reheating (boiling for 30 minutes is ineffective!), the enterotoxin is introduced into the body and carries out its effect in the intestine resulting in severe vomiting and diarrhea. In the Wikipedia entry for Staphylococcal Enterotoxin B, there is an anecdote that the precursor of the U.S. Central Intelligence Agency utilized a vial of the exotoxin to incapacitate a Nazi agent prior to the D-Day invasion of Normandy, however that story is uncited and my Search-Fu cannot turn up an independent report.
Other toxins are more worrisome! The members of genus Clostridium are potent toxin producers, and some of the toxins have lethal doses in the nanogram (10-9 gram) ranges. All Clostridium species are strict anaerobes and are intolerant of atmospheric oxygen concentrations. All Clostridium species are endospore formers. They are not found in the human bodies in the absence of disease, with the exception of Clostridium difficile, which is a minor component of the human intestinal flora. Here is a summary of the major Clostridial exotoxins:
- Clostridium difficile: The toxin causes pseudomembranous colitis, or inflammation of the colon, leading to severe diarrhea. Development of disease is associated with broad-spectrum antibiotic use, which leads to depletion of the normal microbial flora that keeps this organism in check. Cessation of the antibiotic in question typically allows resolution of the signs and symptoms, as the normal flora begin to recolonize the colon. Supportive and palliative therapies are advised.
- Clostridium botulinum: One of the most toxic neurotoxins known to medicine. The toxin prevents the release of the neurotransmitter acetylcholine from neuromuscular junctions, preventing the contraction of voluntary muscles. Toxemia causes the patient to exhibit “flaccid paralysis,” which will require supportive therapy until the toxemia passes, however the potency of the toxin leads to a high mortality rate. Patients may need to be placed on ventilator support, as their diaphragms will be unable contract and allow their lungs to function. Antitoxin therapy (administration of antisera reactive with the toxin) will help to eliminate the toxin from the body.
- Clostridium tetani: Another neurotoxin that is very potent and has a high mortality rate (40% if untreated.) Unlike botulinum toxin, tetanus toxin affects only the inhibitory neuromuscular junctions. In this case, muscles are able to contract, but the toxin prevents them from relaxing. Toxemia causes the patient to exhibit “rigid paralysis,” that continues to develop as muscle groups tighten. In the case of the upper limbs, the strength of the bicep overpowers the tricep muscle, leading to a very characteristic clenching of the body. Patients again will be needed to be placed on supportive therapy until the toxemia passes, frequently requiring ventilator support. Antitoxin therapy again can help eliminate the toxin from the body.
Hopefully this helps to summarize what some of these toxins do. What do you think?