Disease/Toxins
Tetanus and botulism toxins are proudced by anaerobic bacteria from the genus Clostridium. The toxins are produced by different bacteria but both of the toxins have zinc-dependent endoproteinase action. They are large proteins 150 Kda that consist of:
- light-chain – contains metallo-endopeptidase domain.
- heavy-chain – receptor binding domain required for internalisation.
The bacteria secrete the toxins that target the SNARE complexes at the nerve terminals. The toxins inactivate the SNAREs by cleaving them, this results in a block of vesicular release and at synapses in the brain and at the neuromuscular junction it blocks neurotransmission.
The diagram below show a culture of the bacteria Clostridium botulinium:
Follow this link to a picture of a culture of the bacteria clostrium tetani that causes tetanus:
www.adacelvaccine.com/Images/protect/adacel/tetanus.gif
Botulism Toxin
There are 7 different toxins named A-G produced by the anaerobic bacteria C.botulinum, the condition botulism is caused by the toxins and is characterised by weakness and paralysis of skeletal muscles as well as a host of symptoms related to blocking acetylcholine release, a neurotransmitter widely used throughout the body. The different forms of the toxin target different SNAREs, the condition botulism is caused when the toxins cleave their specific SNARE:
- BoNT A – SNAP 25.
- BoNT B- synaptobrevin1 and 2.
- BoNT C1- syntaxin and it is suggested but proven it interacts with SNAP25. There are four isoforms of synatain A and B both of which are neuronal are targeted by the toxin.
- BoNT D – synaptobrevin 1 and 2.
- BoNT E - SNAP 25.
- BoNT F – synaptobrevin 1 and 2.
- BoNT G – synaptobrevin 1 and 2.
Botulism can be contracted by ingestion and is often due to food poisoning. The spores from the bacteria can survive boiling temperatures for a number of hours. The bacteria can reproduce in food at room temperature and secrete the toxin. Botulinal toxins can bind with other proteins in the gut to resist degradation, so that they are absorbed intact. Once absorbed the toxins get transported around the body via the lympathtic system and bind to neurons in the spinal cord to block all neurotransmission.
The first symptoms caused by the toxin are related to inhibition of acetylcholine release in the autonomic nervous system and include a dry mouth, double vision and difficulty in speaking and swallowing due to the onset of muscle paralysis. Weakness and paralysis of muscles in the limbs and gastrointestinal follow and eventually respiratory muscles are paralysed so that death is caused by the inability to breathe.
Tetanus Toxin
Tetanus toxin is produced by the anaerobic bacteria Clostridium tetani and the toxin can be referred to as tetanospasmin There is only one type of toxin unlike botulism toxins, it is abbreviated to TeTx and it targets synaptobrevin 1 and 2 of the SNARES. It acts by blocking the release of glycine. Glycine is an inhibitory neurotransmitter released by motorneurons and inhibitory interneurons, this results in a lack of inhibition of muscles and therefore the muscles are overly contracted. The muscle contraction often starts with the muscles of mastication and so tetanus is colloquially called “Lockjaw”.
The toxin gains entry to the organism by wound or puncture of the skin, it then travels along the peripheral nerves to the spinal cord where the majority of the attack occurs. At the spinal cord it inhibits the inhibitory interneurons effect by blocking the release of glycine. The Tetanus toxin mainly affects the release of the neurotransmitter glycine and its action is similar to that of botox. Tetanus blocks the release of acetylcholine at the neuromuscular junction as well.
There is a vaccine for tetanus so in the west and modernised societies tetanus is a rare condition. However it is still rife in third world countries which Unicef is hoping to tackle by introducing a vaccination programme in conjunction with Pampers – See article in the news section on the homepage.
Clinical/ therapeutic uses of botoulism toxin.
The understanding of synaptic physiology and identification of the components involved in synaptic transmission were discovered by research using toxins including tetanus and botulism toxins.
Many disease of the central nervous system (CNS) composed of the brain and spinal cord produce an increase in muscle tone. Local injury or arthritis can also have the same effect as can brain damage at birth causing cerebral palsy. In addition chronic back pain in some cases can be cause by muscle spasm.
There are many used for botox that include:
- Strabismus - more commonly desribed as "cross- eyed" this can be treated by treatind the extraocular muscles requires.
- Cervical dystonia - this condition causes neck muscles to contract involuntarily resulting in abnormal movements of the head and neck.
- Blepharospasm - this is a disorder that causes involuntary contraction of the eye muscles paralysis of the muscles prevents them twitching.
- Hyperhidrosis - more commonly known as "excess sweating" this can also be treated with botox because the autonomic nervous system using acetylcholine is blocked when it normally controls activation of sweat glands.
Botulism toxin can be injected into the affected muscles to relieve increased muscle tone by causing paralysis confined to the site of administration. Botox is the drug name given to purified botulism toxin used for these kind of procedures. However Botox is just a local treatment other drugs can be used to treat all muscle but these generally have side-effects that can include drowsiness and confusion.It is now common for Botox to be used cosmetically to paralyse facial muscles to reduce wrinkles and signs of ageing. The injection of small amounts is believed to be entirely safe but recent research as shown that the toxin can escape from the facial muscles into the brain in rats.
The video above gives an overview of the mechanism of action of the botulism toxin
The link below is to a website that shows in more detail the action of the botulism toxin: