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IMIN 200 > Bacterial Toxins > Flashcards

Bacterial Toxins Flashcards

1
Q

What are bacterial toxins and what do they do?

A

Poisonous substances produced within bacteria and promote infection and disease by directly damaging host tissues and by disabling the immune system

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2
Q

Which strains of bacteria can produce toxins and are they general or specific to the species?

A

Virulent strains
Specific to the species

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3
Q

What are the effects of DT in vivo?

A

Inhibits protein synthesis leading to epithelial cell damage and myocarditis

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4
Q

What are the effects of CT in vivo?

A

Activates adenylate cyclase, elevates cAMP in cells leading to changes in intestinal epithelial cells that cause loss of water and electrolytes

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5
Q

What are endotoxins, typically what is the Gram stain, and what effects do they have?

A

The part of the bacteria that is toxic to the host
Gram-negative
Generalized effect

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6
Q

What are exotoxins, typically what is the Gram stain, and what effects do they have?

A

Secreted toxins with high potency that have specific effects
Mostly Gram-positive

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7
Q

What is an example of an endotoxin?

A

Bacterial LPS lipid A
Release of lipid A in small amounts overwhelms the TLR4 pathway which induces massive inflammation

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8
Q

What are the 3 main types of exotoxins?

A

AB toxins
Pore-forming toxins
Super antigens

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9
Q

How do bacterial toxins (exotoxins) resemble enzymes?

A

Protein-based
Denaturable
Catalytic activity
Have a degree of specificity

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10
Q

Which routes does DT use to enter host cells?

A

Direct entry and RME

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11
Q

What is direct entry and which toxins use it?

A

The binding of the B subunit of the toxin forms a pore to allow entry of the A subunit
Some AB toxins

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12
Q

How does DT enter a host cell via RME?

A

The B subunit binds endogenous receptors on the host
The entire toxin is internalized into a vesicle inside the host
The vesicle is transported to the endosomes where the low pH causes the A/B toxin to dissociate
The A subunit leaves the endosomes and enters the cytoplasm

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13
Q

What are AB toxins and what do they do?

A

Two-component protein complexes secreted by a number of pathogenic bacteria that interfere with internal cell function

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14
Q

What is an A+B toxin?

A

The toxin is synthesized and secreted as two independent subunits

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15
Q

What is an A-B toxin?

A

Components are synthesized separately but associate during secretion

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16
Q

What is a 5B toxin?

A

The B subunit is composed of 5 identical B subunits, synthesized separately

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17
Q

What is a 5B toxin?

A

The B subunit is composed of 5 identical B subunits, synthesized separately

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18
Q

What is an A/B toxin?

A

Components are synthesized as a single polypeptide then cleaved into subunits

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19
Q

What type of AB toxins are PT and CT and how do they enter the host?

A

5B, RME

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20
Q

What type of AB toxin is DT and how does it enter the host?

A

A/B, RME and to a lesser extent direct entry

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21
Q

Which receptor that DT bind to on the host cell?

A

HP-EGF receptor (growth factor)

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22
Q

What are the subunits of DT held together by and how are those bonds broken?

A

disulfide bridges and they are broken by host cell receptors

23
Q

What does subunit A of DT do in the cytoplasm of the host cell?

A

Binds to and ADP-ribosylates E2F (elongation factor in transcription) which will halt protein synthesis and kill the cell

24
Q

What is DT encoded by?

A

A prophage which is an integrated bacterial virus and only strains with the phage are virulent

25
Q

What is ADP-ribosylation and what is it required for??

A

The addition of one or more ADP-ribose moieties to a protein required for the initiation of disease

26
Q

What covalently links ADP-ribose to its target?

A

Subunit A

27
Q

What disease does B. pertussis cause, what is it secreted by, and how can it enter the host?

A

Whooping cough
Type IV secretion system
RME or direct entry

28
Q

What type of toxin is PT?

A

An ADP-ribosylating AB5-type toxin

29
Q

What is the mode of action of PT?

A

A subunit ADP-ribosylates a regulatory G protein - target = inhibitory G protein

30
Q

How does PT affect cAMP function and what does it cause?

A

It upregulates cAMP which causes insulin release (hypoglycemia) and cytokine release

31
Q

How does PT enter the host and what does it do when it does?

A

A subunit can enter via RME or direct entry and PT ADP-ribosylates the alpha subunit of Gi

32
Q

What does the B subunit of PT recognize?

A

Several different targets and acts independently as a functioning toxin

33
Q

What is the main symptom of cholera and what is the toxin encoded by?

A

Watery discharge/diarrhea
Prophage

34
Q

What do the 5B subunits associate into in CT?

A

A barrel structure that is often heavily glycosylated

35
Q

What does heavy glycosylation allow?

A

Immune evasion and increased host range

36
Q

What is CT secreted by?

A

Type II secretion system

37
Q

What else does CT secrete?

A

A neuraminidase enzyme which removes sialic acid from the host cell receptor to facilitate CT binding

38
Q

Where does cholera colonize?

A

The small intestine

39
Q

What is CT produced in response to and which receptor does it associate with?

A

Infection and associates with a GMI receptor (ganglioside receptor localized in lipid rafts of enterocytes

40
Q

How does CT move from endosomes to the ER?

A

Via retrograde transport

41
Q

How does CT get to the cytoplasm?

A

CT is internalized by RME
At ER, A subunit leaves the endomembrane system and enters the cytoplasm via sec61 endogenous transporter
Unfolds during transport and refolds in the cytoplasm

42
Q

Mode of action of CT?

A

Refer to notes

43
Q

What is KDEL?

A

A 4 aa sequence in CT that acts as a euk endogenous ER retention signal

44
Q

Where is KDEL located and where does it bind?

A

At the carboxyl terminus of the CT A subunit and it binds to Erd2 in the Golgi

45
Q

What does binding at the KDEL sequence cause?

A

Euk host to traffic toxin from endosomes to ER

46
Q

What are pore-forming toxins?

A

Protein exotoxins (secreted)

47
Q

What do pore-forming toxins do?

A

They are cytotoxic and created unregulated pores in the membrane of targeted cells

48
Q

What do PFTs insert into a host cell membrane?

A

A transmembranous pore

49
Q

What do PFTs disrupt and what are they secreted by?

A

Disrupt selective permeability of the host
Secreted by the pathogen and assemble at the host cell membrane

50
Q

What is a pre-pore intermediate and what does it do?

A

Pore components associate and assemble at the membrane prior to insertion
Beta-toxin
Causes an efflux of nutrients from the host

51
Q

What is a partially-formed pore?

A

Assembly of the PFT is simultaneous with insertion
Alpha-toxin

52
Q

What are examples of pre-pore intermediates and partially-formed pores?

A

Pre-pore = C. perfringens
Partial = S. aureus

53
Q

How do partially-formed pores work?

A

PFT subunits bind to host cell membrane via specific interactions - lipids or proteins

54
Q

What happens at an active PFT?

A

Toxin accumulates and oligomerizes

IMIN 200 (23 decks)

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