Botulinum Toxin Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

What type of bacteria causes botulism?

A

Gram-positive, anaerobic bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What main species of bacteria causes botulism?

A

Clostridium botulinum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the two forms of Clostridium botulinum and which form is the infectious agent?

A
  • Vegetative (rod shaped, but robust)
    • infectious form
  • Spore (long lasting)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where can Clostridium botulinum be found?

A

In decomposing carcasses and spoiled feed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where does Clostridium botulinum attack in the body and what is the overall result in its host?

A

The neuromusclar junction on the neuron causing flaccid paralysis. The bacteria does NOT affect the muscle themselves.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What mediates Clostdridium botulinum infection and where is it produced in the body?

A

Mediated by botulinum toxin (BoNT)
which is produced in the gut.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the botulinum toxin first produced as and what does it then become?

A

Produced as a single protein that is then cleaved to produce a light chain and a heavy chain linked by disulfide bond.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What chain is the protease part on the botulinum toxin?

A

Light chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What chain is the pore and binding part of the botulinum toxin on?

A

Heavy Chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What chain of the botulinum toxin is the actual toxic part?

A

The light chain is where the protease is located.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are NAPs, what components do they include and what is their role in regards to the botulinum toxin?

A

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 well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How many different serotypes of BoNTs are there, what are they based upon and which can C. Botulinum produce?

A

There are 7 serotypes that are based upon the different light chains and the combinations of toxins/NAPs.

C. Botulinum can produce all seven.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

List the proposed mechanisms/steps (3 steps) of how the botulinum toxin gets from the gut to the blood.

A
  1. Transcytosis: toxin is endocytosed by epithelial cell and exocytosed on the basilateral side
  2. 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.
  1. Absorption from damaged epithelial barrier
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does the c-terminal of the BoNT heavy chain bind and where on the neuron?

A

Binds to polysialogangliosides in lipid rafts on the presynaptic terminal of the neuron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

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.

A

Additional co-receptors may be required, like Thy1 or synaptotagmin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens when the botulinum toxin binds to the neuron?

A

The toxin is then internalized into presynaptic terminal by endocytosis.

17
Q

What results from the acidifcation of the endosome formed from the internalization of the botulinum toxin?

A

Converts heavy chain into a pore that allows the release of the light chain into the cytoplasm. (light chain is the toxic part - protease)

18
Q

Specifically what is the light chain of the botulinum toxin and what does it target and cleave?

A

The light chain is a zinc-endopeptidase that targets and cleaves SNARE proteins (machinery involved in neurotransmitter release). Different light chains target and cut different SNARE proteins.

19
Q

List and describe the two types of SNARE proteins and give examples of each.

A
  • V-SNAREs - synaptobrevin (VAMPT)
    • located on vesicles that contain neurotransmitter
  • T-SNAREs - syntaxin, SNAP25
    • located on plasma membrane of terminal
20
Q

SNAREs are required for ….

A

the binding and fusion of presynaptic vesicles to the plasma membrane for neurotransmitter release. They pull vesicles to the plasma membrane and lock them in place.

21
Q

What SNARE protein does light chain C cleave?

A

Syntaxin

22
Q

What SNARE protein does light chain A cleave?

A

SNAP-25

23
Q

List the five steps regarding the mechanism of the botulinum toxin effecting the neuron.

A
  1. Botulinum toxin binds to neuron at neuromusclar junction (NOT muscle)
  2. Toxin is endocytosed
  3. Acidification of endosome causes heavy chain become a pore in and release light chain into cytoplasm
  4. Light chain is released into cytoplasm
  5. Light chain depending on serotype will cleave different SNARE proteins to prevent fusion of neurotransmitter vesicles to the plasma membrane