Friday, August 30, 2013

Tetanus and Botulinum...How they act

We are used to hearing about tetanus and botulinum but, what are we really talking about?  How do they act in our body? 
Clostriudium tetani and Clostriudium botulinum are two types of anaerobic organisms which produce spores and are part of the Bacillaceae family. Their capacity of spore production make them possible to live even in the presence of oxygen. The effects of toxins can go unnoticed until they start producing two powerful neurotoxins capable of causing different sorts of neurological syndromes. Let us take a close look at the way these powerful toxins act in our body. 

C. tetani spores can be found in the ground and can contaminate the wounds. When it exists a low presence of oxygen, especially with covered or infected wounds, the spores re-create the bacteria from which they have emerged by a process called germination. The bacteria is thereby active again and it can synthesize the neurotoxin. In this case it is called tetanospasmin. This toxin is produced as one single polypeptide, which is activated by an endopeptidase through a process called proteolysis and it creates two different fragments: a protein subunit α (light chain) and a protein subunit β (heavy chain), both joined by a disulfide bond. When tetanus toxin is located inside our body, the lymphatic vessels carry it through the nerve fibers. The toxin binds to the membrane of motor neurons α since it exists a correlation between heavy chain β and GM2 receptor, which is present in this type of neurons. Inside the neurons, the toxin is carried through the anterior horns of the spinal cord by using the dynein and then through the inhibitory interneurons via trans-synaptic. These have the function of inhibiting the motor neuron action by the release of inhibitory neurotransmitters. At this point it acts the protein subunit α, which contains zinc endopeptidase and are able to attack SNARE proteins necessary to release the neurotransmitters. As a result, there is a lack of inhibition of motor neurons, it causes a simultaneous spasm in agonist muscles and antagonists muscles (spastic paralysis) producing muscle rigidity and convulsions. This is called tetanus.  The symptoms can occur within 4 to 15 days since the wound is created (incubation period). The most common symptom is called trismus, that is the contraction of the masseter muscle, since the distance to the facial nerves is shorter, thus causing the "Risus sardonicus". This contraction affects the muscles around and causes generalised muscle spasms which manifests as opisthotonus, an exaggerated contraction of muscles of the back. More than 90% of the patients without a treatment die and the main reason is the paralysis of muscles of respiration.

There is a similar bacteria called C. botulinum, which was named after the latin word for sausage, botulus since most of the cases of botulism are transmitted by consumption of contaminated food. This bacteria can be present either in ground or water. There are seven types of botulinum toxin (identified from letter A to G). Nevertheless, the human being is just susceptible to types A, B, E and F. The toxin A is the strongest poison of the world, 70 µg of toxin A are enough to kill a person weighing 70 kg. This toxin consists of a light chain α and a heavy chain β, like the rest of the toxins, and its action mechanism is similar to the tetanus toxin. The spores grow under anaerobiosis, especially in preserved food, where the toxin is produced and goes inside our body by the consumption of this food. The chain β protects the neurotoxin from the stomach acidity, the intestine absorbs it and then is carried by the blood through the nerve endings where acetylcholine is inhibited without going all the way back to the spinal cord, like C. tetani does.  
Acetylcholine is an important neurotransmitter for muscle contraction, and without it there is an alteration of contractions which produces flaccid paralysis
The effects of this toxin can be noticed within a couple of days after the consumption of contaminated food. The muscles become weaker and it causes respiratory muscle paralysis and, therefore, the death. 
This disease can be prevented by avoiding the growth of spores in the food. In order to do so, the food pH must been acid or the temperature food must been maintained at 4º C (39.2º F) or lower. The food can also be heated up to 100º C (212º F) for 10 minutes in order to destroy the toxin. 
The botulinum toxin is used as a local therapy to treat some disorders such as migraine, asthma, achalasia or even expression lines between eyebrows.  These expression lines, spasms or twitches can be avoided through the flaccid paralysis of facial muscles. 

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Translation made by Alba Daza Molina