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Flashcards in Lecture 3 Deck (19)
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1
Q

What are the two types of organism that use toxins?

A

Venomous; produced by pathogen/predator as a tool to attack their host/prey, and poisonous; produced as a means of defence

2
Q

What are the four Clostridia interactions with humans?

A

C. botulinum; botulism and food poisoning
C. difficlile; pseudamembranous colitis
C. perfringens; gas gangrene, uterine infections
C. tetanus; Paralysis form infected wounds

3
Q

What type of paralysis is caused by Botulinum intoxication?

A

Flaccid paralysis

4
Q

What type of paralysis is caused by tetanus intoxication?

A

Rigid paralysis

5
Q

Describe the clostridium toxins

A

Secreted as 100kD single chain proteins, which are clevaed into heavy and light chains; heavy chian has translocation and binding domains

6
Q

Where is the site of action of the toxins?

A

Both cellular and intracellular, therefore must;
Bind to their target cell
Translocate to the interior of the cell
Find and Modify their intracellular target

7
Q

What role does each domain play?

A
Heavy chain binding domain (Hc); extracellular binding domain 
Heavy chain translocation domain (Hn); translocation domain 
Light chain (LC); enzymatic domain
8
Q

What does the Hc domain bind to?

A

Ganglioside; Carbohydrate modified sphingolipids found on the external leaflet of the plasma membrane

9
Q

How do clostridial toxins intracellularise?

A

via endocytosis, possibly through interaction with synaptotagmin

10
Q

How is the LC then released?

A

pH dependent membrane translocation; Hn threads the LC out into the pre synaptic terminal

11
Q

How was the role of LC shown?

A

Mochida
Inject LC mRNA (so no heavy chain is present) and see that the toxin inhibits synaptic transmission; probably though accumulating the vesicles

12
Q

Which neurons do they target?

A

BoTx targets motor neurons
TeTx targets inhibitory spinal inter neurons, being take up by motor neurons and then using an endosomal vesicle for trafficking.

13
Q

What homology is seen between the light chains of the Clostridial toxins?

A

Zinc metalloproteinases; which target structures over sequences

14
Q

What is the target for TeTx light chain?

A

Synaptobrevin/VAMP

15
Q

What proteins do the Clostridium toxins target?

A

Proteins that hold the vesicle at the plasma membrane; synaptobrevin, SNAP-25 and syntaxin

16
Q

Which BoTx cleave which targets?

A

C cleaves syntaxin
A, C and E cleave SNAP-25
B, D, G and F cleave Synaptobrevin

17
Q

Why can treatment with toxins that cannot cleave a protein block its cleavage by a toxin that could cleave it?

A

All clostridium toxins are metalloproteinases and will target the SNARE complex; If the toxin cannot cleave it will still be bound to the protein; blocking cleavage by other toxins

18
Q

What is the SNARE hypothesis?

A

SNARE proteins on vesicles decide where the fusion will happen

19
Q

What is a transglutaminase?

A

An enzyme that covalently links proteins that have glutamate