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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?

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?

24
What's proportion of cases occurs in children and elderly?
5-10%
24
What's the difference between STx, STx1, and STx2?
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
Small proportion of survivors develop chronic kidney disease
-N/A-
26
What do shiga toxins do?
- 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
What disease does shiga toxin cause if it binds in the digestive tract?
Causes physical damage unlike cholera, causes bloody diarrhea
28
What disease does shiga toxin cause if it binds in the kidney?
Causes physical damage unlike cholera, causes HUS (kidney failure)
29
What cell receptor does the shiga-like toxin bind to?
Gb3
30
Which animals don't have receptors for shiga-like toxins, making them resistant to toxic effects by shiga toxins?
Cattles, swine, deers
31
Which family are shigatoxins part of? What does each subunit do?
AB5 family toxin A - enzymatic activity 5* B - binding and entry through Gb3 receptor
32
What is the route of shiga toxin?
Cell surface to cytosol via golgi and ER
33
Explain the pathway whereby shiga toxins lead to no protein synthesis
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
Explain the pathway whereby shiga toxins lead to blood clots
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
Explain the pathway whereby shiga toxins lead to increased endothelial inflammation
Shiga-like toxin binds to Factor H Prevents inactivation of C3b Persistent C3b activity Increased alternative pathway complement activation Increased endothelial inflammation
36
How do pore forming cytolysins kill cells?
Form a pore in the cell membrane, induction of apoptosis
37
What cells do haemolysins target?
RBCs
38
What are some reasons bacteria produce toxins that destroy host cells?
Spreading - destroy tissue to help bacteria move Immune evasion - killing of immune cells Nutrition - RBCs carry haem which is important for growth
39
What are exoenzymes?
Proteins secreted by microbes. i.e. lipases, proteases, DNAse, Hyaluronidase, etc
40
What is Zn-metallophospholipase C involve in? (exoenzyme)
Spreading factor, involved in invasive disease - myonecrosis.
41
What is sphingomyelinase C (beta toxin) involved in?
Immune evasive factor, destroys leukocytes
42
What do these lipases do? (mechanism)
Cut the 'phospholipase C' group in the lipid bilayer.
43
What disease do shigatoxins cause due to the destruction of cells?
Clostridial myonecrosis aka Gas Gangrene
44
What do elastases do?
Degrade collagen, elastin, and other host proteins such as IgG, complement, and chemokines
45
PROTEASES???S??S

Medsci 203 (my own) (18 decks)

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