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Microbiology > 3. Tetanus Toxin & BoTox > Flashcards

3. Tetanus Toxin & BoTox Flashcards

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Biology 101 flashcards
1
Q

What are toxinoses (intoxications)? Give examples

A

Disease caused by toxin (little or no colonisation)
E.g.
- Botulism/tetanus - Clostridium botulinum/tetani (A-B toxin)
- Food poisoning - Clostridium perfringens (pore-forming toxin)
- Toxic shock - Staphylococcus aureus (superantigen)

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2
Q

True or False: Clostridium tetani itself causes tetanus

A

False - the toxin it produces causes tetanus

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3
Q

True or False: Clostridia is a very diverse genus

A

True

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4
Q

Are all Clostridia pathogenic?

A

No

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5
Q

What is the vaccine against tetanus?

A

A toxoid - toxin is taken and purified → inactivated using chemicals → vaccine injected into kids → Antobodies produced against tetanus toxin

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6
Q

What bacterium produces the toxin that causes tetanus?

A

Clostridium tetani

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7
Q

What bacterium produces the toxin that causes botulism?

A

Clostridium botulinum

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8
Q

Describe Clostridium tetani & Clostridium botulinum

A

Gram positive, spore formers, strictly anaerobic (absolutely cannot grow in the presence of oxygen)

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9
Q

Where is the botulinum toxin commonly found?

A

Toxin produced in food (or wound), often canned foods, foods with areas of anaerobiosis

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10
Q

What is a bulged can of food an indication of?

A

That bacteria is growing

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11
Q

How common is botulism? What is the fatality rate?

A

Rare - about 25 cases per year in US. Around 10% fatality

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12
Q

Who are particularly susceptible to botulism?

A

Infants

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13
Q

Botulism symptoms?

A

Flaccid paralysis, blurred vision, inability to swallow, difficulty speaking, descending weakness of skeletal muscles & respiratory paralysis

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14
Q

How common is tetanus? What is the fatality rate?

A

750,000-1,000,000 cases per year, around 50-70% fatality

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15
Q

How do most cases of tetanus arise?

A

From small puncture wounds or lacerations which become contaminated with C. tetani spores that germinate & produce toxin

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16
Q

True or False: A large amount of C. tetani spores are needed for severe reaction

A

False - only a small amount are needed

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17
Q

What is the main symptom of tetanus?

A

Spasmic contraction of muscles (in contrast to botulism) - ‘lockjaw’

18
Q

How does Clostridia spread?

A

It will not grow & replicate - not colonisation. The spores will germinate

19
Q

What are the 3 most poisonous substances known to man?

A

Botulinum toxin, tetanus toxin, diphtheria toxin (all are A-B toxins)

20
Q

LD50 for BoNT and TeNT?

A

1 ng/kg

21
Q

C. botulinum can produce a family of bot toxins. What are they?

A

Toxin types A, B, C, D, E, F, G
Toxin types A & B are more commonly assoc. with humans in US & UK
Toxin type E - fish in Japan & Middle East

22
Q

What is the A subunit of Clostridia?

A

Zinc binding metalloprotease - specifically cleaves proteins involved in synaptic fusion

23
Q

Clostridium tetani toxin mechanism?

A
  • Synaptosome (lipid enclosed vacuole) contains NT
  • Synapse fuses with neuron wall → NTs released into synpatic cleft → NTs bind → muscle contracts
  • C. tet toxin prevents release of inhibitory NTs (e.g. GABA) → overstimulation → hypertonia with no control → spasmic contraction
  • Tetanus toxin works in CNS and functions to block release of inhibitory NTs
24
Q

Clostridium botulinum toxin mechanism?

A
  • Toxin binds neuron, tropism dictated by B subunit
  • After endocytosis, B subunit transfers A subunit across membrane & into cytoplasm
  • Active A subunit (zinc metalloprotease) cleaves target protein
  • Different botulinum toxins attack different proteins (SNAP, VAMP, synaptobrevin)
  • C. bot toxin prevents fusion of synaptosome with neuron surface → no contraction → paralysis
  • Treatment: tri- or hepta-valent antitoxin; BIG-IV (BabyBIG)
25
Q

Which is more fatal: botulism or tetanus?

A

Tetanus

26
Q

What are the 2 roles that the B subunit plays in toxin delivery?

A
  1. It has to bind to target cell

2. It has to translocate A subunit into target cell

27
Q

What does tetanus toxin attack?

A

Synaptobrevin II

28
Q

What is botulinum toxin specific for?

A

Peripheral nerve endings - it blocks the release of NTs like ACh, leading to flaccid paralysis

29
Q

What is blepharospasm?

A

Uncontrolled blinking - generally affects older people. Can be treated by injecting BoTox into eyelids

30
Q

Tetanus toxin (Tetanospasmin) is specific for?

A

Presynaptic inhibitory nerve endings (found in CNS) (e.g. GABA)

31
Q

Similarities between Tetanus toxin & BoTox?

A

Both zinc metalloproteases, both simple A-B toxins, both target neurons (are neurotoxins)
Even tho BoTox has a simpler journey throughout the body, both toxins are controlled by the amino acid sequence of its B subunit.

32
Q

Differences between Tetanus toxin & BoTox?

A

Different tropisms - different routes into & through the body
Different targets in nervous system - tetanus toxin has to travel into CNS, whereas BoTox targets peripheral nerves (quite accessible)

33
Q

Normal tetanus exposure is through a puncture wound. How does it get from the muscle to the CNS?

A

Long journey controlled by amino acid sequence of B subunit. B subunit makes sure toxin gets from muscle into blood, across endothelial barrier into body cavity, to a nerve, and then binds to end of nerve (in the periphery). B subunit makes sure that the endosome containing tetanus toxin undergoes retrograde transport back up through entire length of nerve axon into CNS. It then has to travel effectively & efficiently to inhibitory neural synapses.

34
Q

What is the only virulence factor in Botulism?

A

Toxin production (simple A-B toxin)

35
Q

Who make up the majority of tetanus cases?

A

Neonates

36
Q

Although tetanus toxin is incapable of overcoming host defences, what is one virulence factor that is could practice?

A

Evasion

37
Q

Why shouldn’t you give very young children honey?

A

Because it is a common place to find C. bot spores

38
Q

What does C. tetani use to overcome host defences?

A

The wound

39
Q

What are mobile genetic elements?

A

Plasmids/ transposons/ bacteriophages - pieces of DNA that can move between organisms

40
Q

What gene can only be found on large plasmids in C. tetani?

A

TetX gene

41
Q

Can toxin genes be unstable?

A

Yes

42
Q

Why can’t all strains of C. bot cause botulism?

A

Because they need to have the toxin genes

Microbiology (13 decks)

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