L9 Shigella Flashcards
What disease does the Shigella toxin cause?
Dysentery
How does the Shigella toxin cause dysentery?
Invasion, A-B toxin, T3SS
What is another name for Shigellosis?
Bacillary dysentery
Shigella (genus) sonnei/ flexneri/ boydii/ dysenteriae features?
Gram negative
Rod-shaped
Non-motile
>90% related to E. coli
What is dysentery characterised by?
Diarrhoea with blood & mucous
Does dysentery usually progress to septicaemia?
No
How is Shigella transmitted?
Via water & food
Is Shigella highly infectious?
Yes (ID50 of 100-200)
True or False: Humans are the only known natural host for Shigella
True
Are there antibiotic-resistant strains of Shigella?
Yes
Is there a vaccine for Shigella?
No
Describe the pathogenesis of Shigella
- Attachment: adhesins not identified but may involve the produce of ipaD & ipaB genes
- Invasion: rearrangement of host cell actin filaments → induced phagocytosis (unusual for epithelial cells)
- Growth: activated by pH drop, cells escape from vesicle & grow rapidly in cytoplasm (may be mediated by ipaB)
- Spread (a consequence of actin rearrangement)
Pathogenicity of Shigella is associated with what?
The presence of a large virulence plasmid
Which cells do Shigella not adhere to?
Polarised cells
What is the Type 3 Secretion System (T3SS)?
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
Effector proteins from T3SS interfere with?
Host signalling pathways
Examples of pathogenic bacteria with a T3SS?
Shigella, Salmonella, EPEC, EHEC, Yersinia
How does Shigella use the T3SS?
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.
As well as mediating invasion, what other function does T3SS allow Shigella to do?
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
Is Shigella motile?
No, but it can polymerise host actin to move within and between cells (force generated this way can lead to strong, rapid movement)
What can confirm entry and spread of Shigella?
Plaque assay
Features of the Shiga toxin?
- 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)
- Complex A-B toxin: 1 A (stxA1 or A2), 5 identical B (stxB1 or B2)
Which toxin is the Shiga toxin very similar in structure to and how?
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
When is the Shiga toxin released?
During cell lysis
