2- Verocytotoxin/ Shiga E. coli disease

Question 1

what is the most common strain of E. coli that carries the Shiga toxin?

Answer 1

O157:H7

Question 2

how is E. coli O157:H7 identified in the laboratory?

Answer 2

E. coli O157:H7 can be identified by its growth on sorbitol MacConkey agar

it doesn’t ferment sorbitol = agar remains clear, indicating its presence

Question 3

what are the main routes of transmission for VTEC/ Shiga toxin-producing E. coli? (3)

Answer 3

transmitted through various routes:
- consuming contaminated food and water
- person-to-person transmission
- animal-to-person transmission

Question 4

how do the variations of Shiga-like toxin differ?

Answer 4

differ in their amino acid sequences

Question 5

how is the gene for Shiga-like toxin carried?

Answer 5

carried on a lysogenic virus

Question 6

describe the structure of Shiga-like toxin

Answer 6

type III AB5 toxin

consisting of five B components = allow binding to various receptors

has an enzymatic A component = acts as an N-glycosidase

Question 7

describe the pathogenesis mechanism for Shiga-like toxin

Answer 7

Shiga toxins bind to specific receptors - e.g. Gb3/4 receptors - on the host cell membrane

toxin-receptor complex is internalised by receptor mediated endocytosis

internalised toxin is transported by retrograde/backward trafficking through Golgi to reach the ER

A1 subunit of the toxin binds to ribosomes, blocks protein synthesis causing cellular dysfunction = induces an inflammatory response

membrane-bound proteases cleave the A1 subunit from the rest of the toxin molecule - A1 and A2 subunits dissociate

A1 binds to 28s subunit of the ribosome, inhibits protein synthesis further and worsens cell damage

Question 8

what are the primary tissues and organs targeted by Shiga-toxin producing E. coli (STEC)?

Answer 8

• gut mucosal cells
• kidneys
• CVS & CNS

Shiga toxin closely adheres to gut mucosal cells - from the intestine it enters circulation and affects many organs, especially the kidneys

it also affects the cardiovascular and central nervous system tissues

Question 9

how does Shiga-toxin producing E. coli (STEC) affect the kidneys?

Answer 9

it binds to glomerular endothelial cells in the kidney as cells express high levels of toxin receptors

this leads to kidney damage - the inflammation can contribute to microvascular thrombolysis and inhibiting fibrinolysis

Question 10

what is the suggested route for the transport of Shiga toxin from the intestine to other tissues?

Answer 10

route for the transport of Shiga toxin from the intestine to other tissues is debated

some suggest polymorphonuclear neutrophils are a possible carrier

Question 11

list the haematological symptoms of STEC disease (3)

Answer 11

anaemia
renal failure
thrombocytopenia

Question 12

list the gastrointestinal symptoms of STEC disease (2)

Answer 12

watery diarrhoea
abdominal cramps

Question 13

list the less common neurological symptoms of STEC disease (4)

Answer 13

lethargy
tiredness
convulsions
encephalopathy

Question 14

what are the tests for diagnosing STEC?

Answer 14

• observing clinical signs and symptoms
• haematological and biochemical evidence through specifically identifiable molecules/toxins
• detecting growth of the pathogen in differential/selective media - e.g. in sorbitol MacConkey agar
• PCR for Shiga toxin genes

Question 15

what is the treatment for STEC?

Answer 15

generally supportive - renal dialysis and blood product transfusion

no antibiotics