Shigella Flashcards
Is Shigella motile?
No
Shigella has the same life cycle as?
EIEC- Enteroinvasive E.coli
How to differentiate Shigella from E.coli?
Shigella tends to be a lactose non-fermenter
Shigella does not produce gas when breaking down carbohydrates e.g. glucose fermentation
Shigella is non-motile - has no flagella= H antigen or fimbriae
Shigella classification?
Family: Enterobacteriaceae
Genus: Shigella
Shigella causes?
Shigellosis
Symptoms of Shigella infection?
Diarrhoea which is often bloody
Serious complications of Shigella infection?
Encephalopathy- brain infection
HUS- Hemolytic uremic syndrome
Convulsions
What is HUS?
Hemolytic uremic syndrome
It is the loss of platelets, a low red blood cell count (anaemia) and kidney failure
What Shigella infection can cause HUS?
Shigella dysenteriae
How many known species of Shigella are there?
Four
What are the four Shigella species?
Shigella boydii
Shigella flexneri
Shigella sonnei
Shigella dysenteriae
How many serotypes of Shigella sonnei are there?
Only a single serotype
S.flexneri is usually found where?
Most common in low/middle income countries
S.sonnei is usually found where?
Developed/industrialised countries
S.dysenteriae is usually found where?
Sporadic infection
Usually associated with outbreaks
Rates of S.sonnei increase with?
Increased economic development
How is Shigella transmitted?
Fecal-oral route
Poor sanitation
As a country becomes richer?
Increase in rates of S.sonnei and a decrease in the number of S.flexneri infections
Main differences between Shigella and EIEC?
Shigella does not produce gas as it breaks down carbohydrates
Shigella spp. tend to be lactose fermenters
Shigella is non-motile, lacks flagella and fimbriae
How can Shigella be transmitted?
Fecal-oral route Poor toilet behaviour Contaminated water Flies breeding on faeces can spread the disease Poor sanitation
How infectious is Shigella and propose why?
Very infectious
Infectious dose can range from 10-100 particles
Thought to be highly infectious as it can resist the acidic pH of the stomach
What factors of Shigella contribute to diarrhoea?
Shigella dysenteriae: Shiga toxin
The ShET1 and ShET2 enterotoxins
Where does Shigella establish infection?
In the large intestine
Why is Shigella not a good coloniser?
Lacks fimbriae
What mechanism allows Shigella to overcome colonisation resistance of commensals?
Can produce colicins which are antimicrobial peptides. These colicins can kill the commensal bacteria and reduce competition
What are colicins?
They are antimicrobial peptides
What is LPS?
Lipopolysaccharide
Endotoxin
LPS structure?
O antigen
Core region
Lipid A
What is the O antigen?
The O antigen is made up of repeats of an oligosaccharide unit
How does the O antigen exhibit variation?
The O antigen exhibits variation in the types of sugar present, their arrangement within the O unit and the linkages within and between O units, making lipopolysaccharide one of the most variable cell constituents.
The O antigen for Shigella sonnei is?
Structurally unique
Shigella sonnei has an O antigen almost identical to those present in?
Plesiomonas shigelloides chromosome
O antigen for Plesiomonas shigelloides is encoded on?
A chromosome
The O antigen for Shigella sonnei is encoded on
A plasmid
Why the O antigen of S.sonnei located on a plasmid?
Inactivated the O antigen encoded on the chromosome and acquired a new coding region for the O antigen on a plasmid
How many serotypes of S.sonnei are there?
A single serotype
What is different about the O antigen of S.sonnei?
It is much simpler and shorter
Immunity to S.sonnei in communities with contaminated water supplies?
Many have been provided by Plesiomonas shigelloides infection.
It is thought that Shigella evolved from?
Non-pathogenic E.coli
How did Shigella evolve from non-pathogenic E.coli?
- Gain of a virulence plasmid
- Gain of pathogenicity islands
- Loss of ‘antivirulence’ genes such as ompT and cadA
What is the virulence plasmid?
Encodes virulence effectors
Also encodes the T3SS
Shigella encodes virulence factors on?
The virulence plasmid and chromosomally
What toxin is encoded chromosomally?
ShET1
ShET1 is encoded on?
Pathogenicity island on the chromosome
What are the pathogenicity islands in Shigella known as?
Shigella pathogenicity islands= SHIs
What pathogenicity island encodes ShET1 enterotoxin?
SHI-1
What are two “anti-virulence” genes that have been lost?
ompT and cadA
How does OmpT impede virulence?
OmpT inhibits the spread of Shigella by interfering with the polar localisation of the actin nucleator protein IcsA
What is OmpT?
An outermembrane protease
What is IcsA?
IcsA is an actin nucleator protein
What is the function of IcsA?
It is an actin nucleator protein and is needed for actin polymerisation
IcsA recruits?
Recruits N-WASP which then leads to the recruitment of Arp2/3
What does Shigella use actin polymerisation for?
Uses it for cell-to-cell spread
What does cadA gene encode?
Encodes a lysine decarboxylase
What does lysine decarboxylase (encoded by cadA) do?
Catalyses the production of polyamine cadaverine
What does polyamine cadaverine do?
Inhibits the function of Shigella enterotoxins which lessens the disease
cadA encodes?
Lysine decarboxylase
What does lysine decarboxylase do?
It leads to the production of polyamine cadaverine
Polyamine cadaverine does what?
It inhibits the function of Shigella enterotoxins
Why was Shigella motility lost?
Uncertain
Thought it is because it is not needed for intracellular infection as actin polymerisation is used for cell-to-cell movement
Thought to allow Shigella to evade immune detection e.g. TLR5 recognises bacterial flagellin
Shigella infects which cells primarily?
M cells
What are M cells?
Microfold cells
Part of the specialised epithelium
What do M cells do?
They continuously sample antigen from the gut lumen and transcytose it to the basal cell membrane
Why does Shigella infect M cells?
Needs to reach the basal side of the epithelium so it can infect epithelial cells
Why can’t Shigella infect epithelial cells directly?
Due to the microvilli and thick glycocalyx
The T3SS of Shigella lacks the EspA extension filament of the needle. In EPEC/EHEC the needle of the T3SS is capped by an extension EspA filament which allows penetration through the glycocalyx and into the epithelial cell.
M cells do not have?
They do not have microvilli on their surface
They do not have a thick glycocalyx
How does Shigella reach the epithelial cells?
Reaches the epithelial cells via the filopodia
What are filopodia?
Cell surface sensory organelles
What does the eukaryotic cell use filopodia for?
Sensing, migration and cell-cell interaction
What does Shigella use the filopodia for?
Shigella establishes contact with the filopodia-like extensions, which retract to bring bacteria in contact with the cell body where invasion occurs
Once the Shigella has been transcytosed it is?
Taken to the basal cell membrane, where lots of macrophages are present. May be phagocytosed by the macrophages.
How does Shigella enter cells, including M cells?
Membrane ruffling
How do the bacteria escape the macrophages?
By inducing apoptosis
Once released from the dying macrophage what does the Shigella do?
Enters epithelial cells via the basolateral side
How does Shigella enter epithelial cells?
Through membrane ruffling
How does Shigella cause membrane ruffling?
T3SS
Injection of T3SS effectors which reorganise the actin cytoskeleton and leading to the formation of membrane ruffles
How can Shigella move around the cell and to other cells if it is non-motile?
By utilising host cell actin polymerisation
What is needed for actin polymerisation and movement of Shigella?
IcsA
What is IcsA?
An outer membrane protein
Where is IcsA localised?
Polarly
How does actin polymerisation occur?
Polar localisation of IcsA outer membrane protein.
What does IcsA do?
IcsA protein promotes actin nucleation
Recruits N-WASP
N-WASP recruits?
Actin polymerisation Arp2/3 complex
Actin polymerisation process?
IcsA is an outer membrane protein of Shigella
It has polar localisation
N-WASP is recruited
Arp2/3 complex is recruited which results in actin nucleation
Shiga toxin is associated with which shigella species?
S.dysenteriae
Shiga toxin is also produced by E.coli known as?
STEC- shiga toxin producing E.coli
STEC can produce which shiga toxins
Stx1 or Stx2
Which STEC shiga toxin is identical to that produced by Shigella?
Stx1
Shiga toxin structure?
1 A subunit and 5 B subunits
AB5 structur
Shiga toxin binds to which receptor?
Gb3
B subunit binds to?
Gb3 receptor
What does the A subunit do?
The A subunit removes an adenine residue from 28S rRNA which is part of the 60S ribosomal subunit. Prevents protein synthesis from occurring which induces apoptosis
28S rRNA is part of?
The 60S ribosomal subunit
The shiga toxin of S.dysenteriae is produced by?
A dysfunctional/defective prophage
As the phage of S.dysenteriae is defective?
You can treat infection with antibiotics without worrying that more Shiga toxin will be produced. Cannot enter the lytic cycle.
Can you treat EHEC with antibiotics?
No as the prophage encoding Stx will enter the lytic cycle as the antibiotics induce stress in the bacterial cells they occupy
