Diarrhoea Flashcards
What are the 10 methods through which bacteria can cause diarrhoea?
Reduced Cl- absorption through decreasing the surface levels of exchanger
Decreased Na+ uptake by modulating activity of NHE’s
Decreased Na+ uptake by modulating Na+/glucose co-transporter SGLT1
Disrupting aquaporin water channels
Opening tight junctions by phosphorylation of myosin light chain
Directly altering tight junction protein localisation
Disruption of the epithelial barrier function by pro-inflammatory cytokines
What compounds are used to classify E.Coli?
The Lipopolysaccharide which is the O serotype, The flagella which is the H serotype and the capsule which is the K serotype
Is all E. Coli pathogenic?
No many serotypes are commensal but a few strains have picked up virulence genes and cause disease
What is ETEC?
Enterotoxigenic E. Coli
What is EIEC?
Enteroinvasive E. Coli
What is EAEC?
Enteroaggregatvie E. Coli
What is DAEC?
Diffuse-adhering E. Coli
What is EPEC?
Enteropathogenic E. Coli
What is EHEC?
Enterohaemorrhagic E. Coli
What is STEC?
Shiga-toxin producing E. Coli
What is VTEC?
Verotoxin-producing E.Coli
What type of disease is caused by ETEC?
Profuse watery diarrhoea without fever (Travellers diarrhoea)
What type of disease is caused by EIEC?
Mild profuse diarrhoea (can be bloody) and fever
similar to Shigellosis
What type of disease is caused by EAEC?
Watery diarrhoea without fever
What type of disease is caused by DAEC?
Diarrhoea in malnourished children (not in adult volunteers)
What type of disease is caused by EPEC?
Acute diarrhoea, particularly in children
What type of disease is caused by EHEC?
Haemorrhagic Colitis (bloody diarrhoea), haemolytic uraemic syndrome (anaemia and kidney failure)
What type of disease is caused by STEC?
Haemolytic Uraemic Syndrome
What type of disease is caused by VTEC?
Haemolytic Uraemic Syndrome
How does ETEC cause disease?
It has adhesions for attachment and produces a heat-labile enterotoxin which increases cAMP concentrations and heat-stable enterotoxin which increases cGMP concentrations
Both cGMP and cAMP result in activation of CFTR and loss of chloride
How does Enteroinvasive E. Coli cause disease?
It does not produce toxins but it invades the cell and damages the intestinal wall through mechanical destruction as moves through to adjacent cells
How does enteroaggregative E. Coli cause disease?
Produces aggregative adherence factor mediating bacterial-bacterial and bacterial-host attachment
These communities induce IL-8 and produce Serine protease autotransporter- plasmid encoding toxin (Pet) disrupting actin cytoskeleton leading to exfoliation
How does diffuse-adherent E. Coli?
Attachment by afimbrial and fimbrial adhesions these induce IL-8 and autotransporter toxin (Sat)
This results in rearranged brush borders and disrupted tight junctions
How does enteropathogenic E. Coli cause disease?
It is non-invasive and non-toxigenic, instead it uses bundle-forming pilus which mediates initial contact with intestinal cells, then though a type 3 secretion system effector proteins are injected into the host cell causing the microvilli to be lost
What is LEE?
The locus of enterocyte effacement which codes for both the type 3 secretion system and the effector proteins
How does the type 3 secretion system work?
EscC is in the outermembrane of the bacteria, the EspA subunit is then taken to the extracellular environment through EscC which remains attached to the EscC protein to build up a needle to reach the host cell
Once in the host cell EspD/B attaches the needle to the host cell allowing flow of effector molecules from the bacteria to the host
What are the effector proteins released by type 3 secretion system?
The translocated initim receptor (Tir) allowing closer attachement of the bacteria to the host
Many other proteins allowing for functional redundancy, co-operativity and functional redundancy
What is the role of effector proteins from the type 3 secretion system in diarrhoea?
There is loss of SGLT1 directly and by effacement of the microvilli
Increased activity of Na+/H+ exchanger and decreased activity of H+/Na+ exchanger resulting in decreased Na uptake
Decreases in cell surface level of DRA and internalisation via microtubule rearrangement causing reduced Cl- absorption
There is a stimulating phosphorylation of myosin light chain leading to disruption of tight junctions and the epithelial barrier
Alteration in the phosphorylation status and location of occludin and zona occluding disrupting the barrier function
Why can EPEC caused diarrhoea not be treated with oral rehydration salt therapy?
One of the effector proteins causes a loss if the SGLT1 transporter from the enterocyte which is the key transporter that the therapy relies on
What is haemolytic uraemia syndrome?
A condition which typically has an incubation period of 1-10 days, developing 7 days after the first symptoms
There is anaemia caused by destruction of red blood cells, acute kidney failure and low platelet count with a small proportion of survivors developing chronic kidney disease
What was unique about the rare serotype O157:H7 of E. Coli?
It was found to cause the hamburger outbreak in the early 80’s in the USA
It has two key weapons in its arsenal which can disrupt gastrointestinal cells without invading it and produces a shiga-like toxin
Antibiotics must be used carefully with this strain as if the bacteria is lysed then all the toxin will be released making the disease worse
What are the shiga toxins?
STx which is the shiga toxin from shigella dysenteriae
STx1 which is shiga-like toxin 1 from E. Coli and has a one amino acid difference from STx
STx2 which is shiga-like toxin 2 from E. Coli which has a 56% identity with STx and STx1 it is the most common cause of disease
How do the shiga-toxins function?
Binds to the specific G3B receptor found on small human blood vessels such as those in the GI tract and kidneys, this receptor is not found in cattle, swine or deer therefore it is not toxic to them and these species can act as reservoirs
What are the three mechanisms of shiga-toxins?
STx B subunit binds to GB3 in the cell membrane, the A subunit is then transported to the ER and cleaved by a protease, it then becomes enzymatically active removing a single adenine from 28srRNA inactivating the ribosome causing cell death due to a lack of protein synthesis
Or STxB binds to G3B on endothelial cell membranes leading to inactivation of ADAMTS 13 causing multimers of von Willebrands Factor to accumulate on the endothelial cell surface
Or STx binds to factor H resulting in persistence of C3b on the host cell
Why could the ‘hamburger’ disease be renamed the ‘leafy veg’ disease?
The same serotype of E. Coli O157:H7 which caused the hamburger disease outbreak has also been able to enter inside leaves so they cannot be removed by washing
What occurred in the german E. coli outbreak of 2011?
It was a large and deadly E. Coli outbreak which was unusual as it mainly affected women in their 20’s-40’s and there was a very high rate of Haemorrhagic uraemic syndrome
It was not caused by O157:H7 serotype, there was no LEE so it was not a EHEC strain, but it did carry shiga-like toxin 2 and was resistant to multiple classes of antibiotics It was instead a EAEC strain serotyped as O104:H4
How did an EAEC strain cause the deadly 2011 german E. Coli outbreak?
It had three additional plasmids with the biggest being similar to those isolated from a horse and having multi-drug resistant genes
The smallest codes for two genes one is a DNA replication protein
While the middle one coded for aggregative adherence fimbria gene cluster
