Botulinum Toxin Flashcards
What type of bacteria causes botulism?
Gram-positive, anaerobic bacteria
What main species of bacteria causes botulism?
Clostridium botulinum
What are the two forms of Clostridium botulinum and which form is the infectious agent?
- Vegetative (rod shaped, but robust)
- infectious form
- Spore (long lasting)
Where can Clostridium botulinum be found?
In decomposing carcasses and spoiled feed
Where does Clostridium botulinum attack in the body and what is the overall result in its host?
The neuromusclar junction on the neuron causing flaccid paralysis. The bacteria does NOT affect the muscle themselves.
What mediates Clostdridium botulinum infection and where is it produced in the body?
Mediated by botulinum toxin (BoNT)
which is produced in the gut.
What is the botulinum toxin first produced as and what does it then become?
Produced as a single protein that is then cleaved to produce a light chain and a heavy chain linked by disulfide bond.
What chain is the protease part on the botulinum toxin?
Light chain
What chain is the pore and binding part of the botulinum toxin on?
Heavy Chain
What chain of the botulinum toxin is the actual toxic part?
The light chain is where the protease is located.
What are NAPs, what components do they include and what is their role in regards to the botulinum toxin?
NAPs are non-toxic, neurotoxin-associated proteins that associate with BoNTs (botulinum toxin).
They include hemagglutitin (HA) and non-toxic, non-HA proteins.
They protect BoNT from proteases in the gut and are required for passage of the toxin from the gut into the host circulation.
How many different serotypes of BoNTs are there, what are they based upon and which can C. Botulinum produce?
There are 7 serotypes that are based upon the different light chains and the combinations of toxins/NAPs.
C. Botulinum can produce all seven.
List the proposed mechanisms/steps (3 steps) of how the botulinum toxin gets from the gut to the blood.
- Transcytosis: toxin is endocytosed by epithelial cell and exocytosed on the basilateral side
- Barrier disruption: there are two proposed mechanisms in step 2.
- Hemagglutin in protein disrupts the barrier between the epithelial cells, damaging the cell-to-cell adheren junctions.
- Once a few BoNTs get on the basolateral side, they kill the epithelial cells and destroy the barrier.
- Absorption from damaged epithelial barrier
What does the c-terminal of the BoNT heavy chain bind and where on the neuron?
Binds to polysialogangliosides in lipid rafts on the presynaptic terminal of the neuron
Are co-receptors used in the binding of the c-terminal of BoNT heavy chain on the presynaptic terminal of the neuron? And if so, give examples of two coreceptors.
Additional co-receptors may be required, like Thy1 or synaptotagmin.