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Tetanus
Tetanus is a life-threatening neurological disorder characterized by persistent muscle contractions and spastic paralysis. It is caused by Clostridium…
Tetanus is a severe neuromuscular disorder characterized by sustained muscle spasms caused by the bacterium Clostridium tetani.
It is caused when Clostridium tetani spores enter the host through wounds and germinate under anaerobic conditions in damaged or necrotic tissue.
The germinated vegetative cells remain localized at the infection site and proliferate.
These cells secrete tetanospasmin, a two-chain neurotoxin linked by a disulfide bond.
The toxin spreads to motor nerve endings and enters the motor neuron by endocytosis.
It then travels by retrograde axonal transport to the spinal cord in the central nervous system, where inhibitory interneurons take up the toxin.
After endocytosis, the toxin’s chains separate within the vesicle, and the light chain enters the cytoplasm.
The light chain cleaves synaptobrevin, a vesicle protein needed to release inhibitory neurotransmitters such as gamma-aminobutyric acid, or GABA, and glycine.
This prevents the release of inhibitory neurotransmitters. Without inhibition, motor neurons remain overactive, causing sustained muscle contraction or spastic paralysis, which manifests as muscle rigidity, facial spasms, and lockjaw.
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Q1: How does Clostridium tetani cause tetanus?
Clostridium tetani spores enter the body through wounds and germinate into vegetative cells under anaerobic conditions in damaged tissue. These cells secrete tetanospasmin, a neurotoxin that travels to the spinal cord and prevents the release of inhibitory neurotransmitters like GABA and glycine. Without inhibition, motor neurons become hyperactive, causing sustained muscle contractions characteristic of tetanus.
Q2: What is the structure and function of tetanospasmin?
Tetanospasmin is a 150-kilodalton A-B type neurotoxin composed of heavy and light chains connected by a disulfide bond. The light chain is a zinc-dependent metalloprotease that cleaves synaptobrevin, a SNARE protein essential for synaptic vesicle fusion. This cleavage prevents inhibitory neurotransmitter release, disrupting normal motor neuron regulation.
Q3: How does tetanospasmin travel from the infection site to the central nervous system?
After entering motor nerve endings by endocytosis, tetanospasmin travels retrogradely along axons via dynein motors to the spinal cord. The toxin binds to neuronal membrane components including gangliosides and GPI-anchored proteins at the neuromuscular junction. This retrograde transport allows the toxin to reach inhibitory interneurons in the central nervous system.
Q4: Why does tetanus cause muscle rigidity and lockjaw?
Tetanospasmin prevents the release of inhibitory neurotransmitters GABA and glycine from Renshaw interneurons. Without this inhibition, motor neurons become hyperactive and remain continuously active. This unopposed motor activity manifests as muscle stiffness, spasms, lockjaw, facial grimacing, and generalized rigidity throughout the body.
Q5: What role does tetanolysin play in tetanus infection?
Tetanolysin is a hemolysin exotoxin secreted by Clostridium tetani that promotes local tissue damage and helps create an anaerobic environment for bacterial growth. However, its exact role in disease progression remains unclear. The primary neurological symptoms of tetanus are caused by tetanospasmin, not tetanolysin.
Q6: Why are sensory functions preserved in tetanus patients?
Tetanospasmin affects only motor pathways by disrupting inhibitory neurotransmitter release at motor neurons. Sensory neurons and pathways remain unaffected because the toxin specifically targets the motor neuromuscular junction and motor interneurons in the spinal cord. This selective disruption explains why tetanus patients retain normal sensation despite severe motor dysfunction.
Q7: How does the disulfide bond reduction activate tetanospasmin's toxic function?
Acidification within endosomes activates the heavy chain of tetanospasmin to translocate the light chain into the cytosol. Reduction of the disulfide bond linking the heavy and light chains releases the light chain as a free zinc-dependent metalloprotease. This activated light chain then cleaves synaptobrevin, preventing inhibitory neurotransmitter release.