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Microbiology > 8. Shigella > Flashcards

8. Shigella Flashcards

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1
Q

What does Shigella induce in macrophages?

A

Pyroptosis - form of cell death that is triggered by pro-inflammatory signals and associated with inflammation

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2
Q

What disease does the Shigella toxin cause?

A

Dysentery / Shigellosis

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3
Q

How does the Shigella toxin cause dysentery?

A

Invasion, A-B toxin, T3SS

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4
Q

What is another name for Shigellosis?

A

Bacillary dysentery

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5
Q

What are the 4 types of shigella?

A

S. sonnei
S. flexneri
S. boydii
S. dysentariae

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6
Q

What types of shigella are the most common causes of shigellosis?

A

S. sonnei

S. flexneri

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7
Q

What is the most severe type of shigella?

A

S. dysenteriae

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8
Q

List the Shigella (genus) sonnei/ flexneri/ boydii/ dysenteriae characteristics?

A

Gram negative
Rod-shaped
Non-motile
>90% related to E. coli

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9
Q

What is dysentery characterised by?

A

Diarrhoea with blood & mucous

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10
Q

Does dysentery usually progress to septicaemia?

A

No - bacteria don’t usually spread and get into the blood unless a person is immunocompromised

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11
Q

How is Shigella transmitted?

A

Via water & food

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12
Q

Is Shigella highly infectious?

A

Yes (ID50 of 100-200)

3rd most common GI pathogen

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13
Q

True or False: Humans are the only known natural host for Shigella

A

True

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14
Q

Are there antibiotic-resistant strains of Shigella?

A

Yes

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15
Q

Is there a vaccine for Shigella?

A

No

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16
Q

Describe the pathogenesis of Shigella

A
  1. Attachment: adhesins not identified by may involve the produce of ipaD & ipaB genes
  2. Invasion: rearrangement of host cell actin filaments → inject proteins into the epithelial cell to induce phagocytosis
  3. Growth: activated by pH drop, cells escape from vesicle & grow rapidly in cytoplasm (may be mediated by ipaB)
  4. Spread (a consequence of actin rearrangment)
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17
Q

What are the 4 stages of pathogenesis of shigella?

A

Attachment - Invasion - Growth - Spread

18
Q

Pathogenicity of Shigella is associated with what?

A

The presence of a large virulence plasmid i.e they are mobile

19
Q

Which cells do Shigella not adhere to?

A

Polarised cells

20
Q

What is the Type 3 Secretion System (T3SS)?

A

A protein needle-like complex that functions as a bacterial delivery system to inject bacterial proteins (effectors) directly from the bacterial cytoplasm into the host cytosol

21
Q

Effector proteins from T3SS interfere with?

A

Host signalling pathways

22
Q

Examples of pathogenic bacteria with a T3SS?

A

Shigella, Salmonella, EPEC, EHEC, Yersinia

23
Q

How does Shigella use the T3SS?

A

Shigella flexneri uses T3SS to gain entrance to host cell. Carries needle-like structures on its surface that make initial contact with host cell & form a pore in its plasma membrane. Shigella then injects proteins that interact with the actin cytoskeleton.

24
Q

How does Shigella gain entry to the host cell?

A

M cells

25
Q

As well as mediating invasion, what other function does T3SS allow Shigella to do?

A

Kill macrophages - gains entry via M cells, delivered to macrophages.

Effectors secreted by T3SS injected into macrophage, ruptures phagosome, releases Shigella which kills the macrophage by pyroptosis. Shigella releases different proteins later to invade epithelial cells

26
Q

Is Shigella motile?

A

No, but it can polymerise host actin to move within and between cells (force generated this way can lead to strong, rapid movement)

27
Q

What is actin?

A

Cytoskeletal protein

28
Q

What can confirm entry and spread of Shigella?

A

Plaque assay

29
Q

Features of the Shiga toxin?

A

A family of toxins with 2 major types (Stx1, Stx2)

  • Operon located on a phage (i.e. mobile)
  • Only produced by S. dysenteriae (& some E. coli - EHEC)
  • Complex A-B toxin: 1 A (stxA1 or A2), 5 identical B (stxB1 or B2)
30
Q

Which toxin is the Shiga toxin very similar in structure to and how?

A

Very similar in structure to the Cholera toxin, in that it has a pentameric ring of B subunits with associated A, which is cleaved into A1 & A2 domains held together by a S-S bridge, but different sequence

31
Q

When is the Shiga toxin released?

A

During cell lysis

32
Q

What do the B subunits of the Shiga toxin bind to?

A

Globotriosyl ceramide (Gb3)

Followed by endocytosis & nicking to introduce the A subunit

33
Q

What is the main target of the Shiga toxin?

A

Small blood vessels in intestine, kidney & lungs

34
Q

Following Shigellosis GI infection, what two sequelae can occur?

A

Reiter’s Syndrome

Hemolytic Uremic Syndrome (HUS)

35
Q

Symptoms of Reiter’s Syndrome?

A

Joint pain, eye irritation, painful urination, inflammation almost autoimmune-level disorders

36
Q

Roughly what percentage of people infected with Shigella flexneri will develop Reiter’s Syndrome?

A

3%

37
Q

Hemolytic Uremic System (HUS) can occur after what?

A

S. dysenteriae type 1 infection

38
Q

What is HUS characterised by?

A
  • Blood clots in lungs
  • Convulsions may occur in children (rapid temp. elevation or metabolic alterations)
  • Associated with production of Shiga toxin
39
Q

What is IscA role is

Shigella?

A
  • Interact with the host protein called N-WASP which is involved in actin polymerisation
  • Localised to one end of the bacterial cell
  • IscA triggers actin polymerisation allowing Shigella motility
  • Independent virulence factor not part of the T3SS
40
Q

What is the host protein involved in actin polymerisation?

A

N-WASP

41
Q

What part of the host cell interact with?

A

Underside/basolateral surfaces of the mucosal cells

The integrin (receptors) are located there

Microbiology (13 decks)

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