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Medsci 203 (my own) > L17 Exotoxins and degradative enzymes > Flashcards

L17 Exotoxins and degradative enzymes Flashcards

1
Q

What is an exotoxin?

A

Toxin released by the bacteria into the surroundings

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2
Q

How do exotoxins affect cells?

A

Deregulation of cellular processes and cell damage.
Destruction of innate immune components, tissue damage which leads to necrosis.

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3
Q

What are the differences between infectious disease and microbial intoxication?

A

Infectious disease: pathogen colonises body, pathogen causes disease aided by toxins
Microbial intoxication: pathgoen produces toxins ex vivo, or ingests toxin which causes disease.

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4
Q

Microbial intoxication results from…

A

Eating food where bacteria have previously grown and released toxins. i.e. staphylococcal food poisoning (SFP)

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5
Q

Infectious disease results from…

A

Infection with toxin-producing bacteria. i.e. cholera and haemolytic uremic syndrome.

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6
Q

Staphylococcal food poisoning: results from…

A

S. Aureus produces a family of related toxins - heat and protease resistant, able to survive harsh conditions of the stomach.

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7
Q

Staphylococcal food poisoning: onset…

A

Quick onset - few hours

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8
Q

Staphylococcal food poisoning: symptoms…

A

vomitting, diarrhea, stomach cramps

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9
Q

Staphylococcal food poisoning: recovery time?

A

Quick: 1-2 days

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10
Q

Staphylococcal food poisoning: treatment?

A

None required

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11
Q

Staphylococcal food poisoning: molecular mechanism?

A

unknown

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12
Q

Cholera: cause and spread via…

A

Caused by infection of small intestine with bacteria - Vibrio cholera. Spread via faecal-oral route, eating/drinking contaminated foods. Problematic in areas with poor santization infrastructure

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13
Q

Cholera: Symptoms?

A

Most people develop no or mild symptoms. Less than 20% develop acute watery diarrhoea (rice water)

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14
Q

What is “rice water”in context to cholera?

A

Relates to severe fluid loss (0.5-1L per hour) - up to 40L loss per day. Can result in rapid dehydration, easily treatable by rehydration therapy and preventable by vaccine.

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15
Q

Cholera: mechanism?

A

Toxin mediated disease, belongs to AB5 family of toxins. A subunit - enzyme activity. After ER, it leaves to do its job. B subunit - binding and entry of cholera toxin into cell, into the ER.

CT acts intracellularly, causing Cl- secretion out of cell, into gut. No physical damage. Reversible disregulation of cellular processes.

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16
Q

Cholera: cellular mechanism

A

Read notes on notion

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17
Q

What is Citrobacter rodentium?

A

Bacteria used on rats to understand how Enteropathogenic E. Coli (EPEC) works on humans.

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18
Q

What is EPEC?

A

Enteropathogenic E. Coli - makes attaching-facing lesions and doesn’t have shiga toxins. Has 3 secretion system.

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19
Q

What is EHEC?

A

Enterogaemorragic E. Coli is a variant of EPEC. AKA hamburger disease. Produces shigatoxins, has 3 secretion system.

20
Q

How is EHEC transmitted?

A

By faecal-oral route from contaminated meat and vegies

21
Q

What is the incubation period of EHEC?

A

3-8 days

22
Q

What are the symptoms of EHEC?

A

Severe, acute, haemorragic (bloody) diarrhea
Abdominal cramps
Approx 5-10% of infected patients develop haemolytic uremic syndrome (HUS).

23
Q

What is HUS?

A

Haemolytic uremic syndrome - characterised by:
- Anaemia caused by destruction of RBCs - haemolytic anaemia
- Acute kidney failure (uremia)
- Low platelet count

24
Q

What’s the mortality rate of HUS?

A

5-10%

24
Q

What’s proportion of cases occurs in children and elderly?

A

5-10%

24
Q

What’s the difference between STx, STx1, and STx2?

A

STx: Shiga-like toxin from Shigella dysenteriae
STx1: Shiga-like toxin 1 from E. Coli, differentiating from STx by 1 amino acid.
STx2: Shiga-like toxin 2 from E. Coli, 56% similar to STx and STx1. STx2 is the most common cause of human disease.

25
Q

Small proportion of survivors develop chronic kidney disease

A

-N/A-

26
Q

What do shiga toxins do?

A
  • Inflammation of intestinal epithelium
  • Apoptosis and loss of epithelial barrier function
  • Causes cell death via multiple pathways; no protein synthesis, blood clots, increased endothelial inflammation.
27
Q

What disease does shiga toxin cause if it binds in the digestive tract?

A

Causes physical damage unlike cholera, causes bloody diarrhea

28
Q

What disease does shiga toxin cause if it binds in the kidney?

A

Causes physical damage unlike cholera, causes HUS (kidney failure)

29
Q

What cell receptor does the shiga-like toxin bind to?

A

Gb3

30
Q

Which animals don’t have receptors for shiga-like toxins, making them resistant to toxic effects by shiga toxins?

A

Cattles, swine, deers

31
Q

Which family are shigatoxins part of? What does each subunit do?

A

AB5 family toxin
A - enzymatic activity
5* B - binding and entry through Gb3 receptor

32
Q

What is the route of shiga toxin?

A

Cell surface to cytosol via golgi and ER

33
Q

Explain the pathway whereby shiga toxins lead to no protein synthesis

A

B subunit binds to Gb3 receptor on cell surface
A subunit transported to ER
A subunit cleaved by a protease (RNA N-glycosidase) to make enzymatically active
A subunit removes a single adenine from 28s rRNA -> irreversibly inactivates ribsome, inhibiting protein synthesis
Cell death

34
Q

Explain the pathway whereby shiga toxins lead to blood clots

A

B subunit binds to Gb3 in cell membrane
Inactivation of ADAMTS 13 (metalloprotease)
Accumulate multimers of von Willebrand Factor on endothelial cell
Resulting in clumping of platelets
Blood clots

35
Q

Explain the pathway whereby shiga toxins lead to increased endothelial inflammation

A

Shiga-like toxin binds to Factor H
Prevents inactivation of C3b
Persistent C3b activity
Increased alternative pathway complement activation
Increased endothelial inflammation

36
Q

How do pore forming cytolysins kill cells?

A

Form a pore in the cell membrane, induction of apoptosis

37
Q

What cells do haemolysins target?

A

RBCs

38
Q

What are some reasons bacteria produce toxins that destroy host cells?

A

Spreading - destroy tissue to help bacteria move
Immune evasion - killing of immune cells
Nutrition - RBCs carry haem which is important for growth

39
Q

What are exoenzymes?

A

Proteins secreted by microbes.
i.e. lipases, proteases, DNAse, Hyaluronidase, etc

40
Q

What is Zn-metallophospholipase C involve in? (exoenzyme)

A

Spreading factor, involved in invasive disease - myonecrosis.

41
Q

What is sphingomyelinase C (beta toxin) involved in?

A

Immune evasive factor, destroys leukocytes

42
Q

What do these lipases do? (mechanism)

A

Cut the ‘phospholipase C’ group in the lipid bilayer.

43
Q

What disease do shigatoxins cause due to the destruction of cells?

A

Clostridial myonecrosis aka Gas Gangrene

44
Q

What do elastases do?

A

Degrade collagen, elastin, and other host proteins such as IgG, complement, and chemokines

45
Q

PROTEASES???S??S

A

Medsci 203 (my own) (18 decks)

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