8. Shigella Flashcards
What does Shigella induce in macrophages?
Pyroptosis - form of cell death that is triggered by pro-inflammatory signals and associated with inflammation
What disease does the Shigella toxin cause?
Dysentery / Shigellosis
How does the Shigella toxin cause dysentery?
Invasion, A-B toxin, T3SS
What is another name for Shigellosis?
Bacillary dysentery
What are the 4 types of shigella?
S. sonnei
S. flexneri
S. boydii
S. dysentariae
What types of shigella are the most common causes of shigellosis?
S. sonnei
S. flexneri
What is the most severe type of shigella?
S. dysenteriae
List the Shigella (genus) sonnei/ flexneri/ boydii/ dysenteriae characteristics?
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 - bacteria don’t usually spread and get into the blood unless a person is immunocompromised
How is Shigella transmitted?
Via water & food
Is Shigella highly infectious?
Yes (ID50 of 100-200)
3rd most common GI pathogen
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 by may involve the produce of ipaD & ipaB genes
- Invasion: rearrangement of host cell actin filaments → inject proteins into the epithelial cell to induce phagocytosis
- Growth: activated by pH drop, cells escape from vesicle & grow rapidly in cytoplasm (may be mediated by ipaB)
- Spread (a consequence of actin rearrangment)
What are the 4 stages of pathogenesis of shigella?
Attachment - Invasion - Growth - Spread
Pathogenicity of Shigella is associated with what?
The presence of a large virulence plasmid i.e they are mobile
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.
How does Shigella gain entry to the host cell?
M cells
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 is actin?
Cytoskeletal protein
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 - EHEC)
- 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
What do the B subunits of the Shiga toxin bind to?
Globotriosyl ceramide (Gb3)
Followed by endocytosis & nicking to introduce the A subunit
What is the main target of the Shiga toxin?
Small blood vessels in intestine, kidney & lungs
Following Shigellosis GI infection, what two sequelae can occur?
Reiter’s Syndrome
Hemolytic Uremic Syndrome (HUS)
Symptoms of Reiter’s Syndrome?
Joint pain, eye irritation, painful urination, inflammation almost autoimmune-level disorders
Roughly what percentage of people infected with Shigella flexneri will develop Reiter’s Syndrome?
3%
Hemolytic Uremic System (HUS) can occur after what?
S. dysenteriae type 1 infection
What is HUS characterised by?
- Blood clots in lungs
- Convulsions may occur in children (rapid temp. elevation or metabolic alterations)
- Associated with production of Shiga toxin
What is IscA role is
Shigella?
- 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
What is the host protein involved in actin polymerisation?
N-WASP
What part of the host cell interact with?
Underside/basolateral surfaces of the mucosal cells
The integrin (receptors) are located there
