Shigella and Shigellosis Flashcards
Are majority of cases in the developed or developing world? (shigella)
developing
What is the structure, motility and can shigella ferment lactose?
- Gram negative rod
- Non motile
- Non fermentation of lactose
What are the different shigella species and how many serotypes are in each?
- Shigella dysenteriae (group A)
○ 18 serotypes
- Shigella flexneri (Group B)
○ 6 (2) serotypes
- Shigella boydii (Group C)
○ 12 serotypes
- Shigella Sonnei (Group D)
○ 1 serotypeExplain the infective dose of shigella
- Small number of organisms (10-100) can induce disease
- Resistant to gastric acidity
- 10 organisms will cause disease in 10% of population, 100-200 will cause disease in 50% of population
What are symptoms of shigellosis/Bacillary dysentery
- Diarrhoea
- Blood and mucus in stools
- Fever
Abdominal cramps
Where does shigella usually infect?
- Invasive infection of colon and rectum in humans
- Initiates acute destructive recto colitis
What are the clinical diseases associated with each type of shigella? What is the outcome of clinical disease
- Shigellosis
○ Ranges from mild diarrhoea -> severe dysentery
○ Frequent passage of bloody mucoid small stools - Haemorrhagic colitis
○ Invasion of colonic mucosa
○ Degeneration of epithelial cells and acute inflammation of lamina propria
○ Desquamation and ulceration - Outcome: generally self limiting condition but can be life threatening in children due to dehydration and chronic malnutrition
What is the invasion strategy of shigella?
- Enters M cell and is taken up by a macrophage
- Kills macrophage (apoptosis) and enters epithelial cells from the sub-mucosal layer
- Also sends IL-1B to epithelial cells which allow for bacteria to be taken in
Explain where shigella carries virulence genes
- Plasmid - carries structural genes for adherence, invasion and cell to cell spread
- Chromosomal - regulatory genes, Intracellular growth
What is the essential virulence gene cluster that must be present? (shigella)
Pathogenicity island (pINV)
What are the genes in a shigella flexnerii pathogenicity island?
- Type III secretion system
○ Spa - surface presentation of antigen
○ Mxi - membrane excretion of invasion plasmid antigen - Invasion plasmid antigen (Ipa)
How does Shigella Flexnerii invasion work? What are the key proteins and their role?
- When there is contact of shigella to host cell, Mxi-spa apparatus is activated which delivers bacterial invasins (Ipa) into the host cell
- Multiple genes help with this (in slides)
- Attachment and entry of Ipa protein leads to extensive cytoskeletal rearrangement
○ Pseudopod formation
○ Engulfment of shigella (entry into epithelial cell)
○ Escape vacuole (IpaB/C) (Multiplication)
How does Shigella spread cell to cell?
Actin based motility
Explain Actin based motility (shigella)
- Production of IcsA which encodes an outer membrane protein
○ This protein is localised at pole of bacterium, expression directs actin based motility, deposition of F actin confers a motive force to bacteria which leads to intracellular spread - The amount of IcsA on the surface of shigella determines whether tail assembly occurs (lots of IcsA leads to assembly of actin tail and movement)
Summarise the intracellular life of shigella
- Bacteria is internalized in primary vacuole
- Secretion of bacterial escape proteins
- Disruption of vacuole membrane
- Actin polymerization and replication
- Cell protrusion
- Internalization in secondary vacuole
- Secretion of bacterial escpae proteins
- Disruption of - double-membrane vacuole
- Replication in cytosol
