Bacterial Toxins

Question 1

What are bacterial toxins and what do they do?

Answer 1

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

Question 2

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

Answer 2

Virulent strains
Specific to the species

Question 3

What are the effects of DT in vivo?

Answer 3

Inhibits protein synthesis leading to epithelial cell damage and myocarditis

Question 4

What are the effects of CT in vivo?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

What is an example of an endotoxin?

Answer 7

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

Question 8

What are the 3 main types of exotoxins?

Answer 8

AB toxins
Pore-forming toxins
Super antigens

Question 9

How do bacterial toxins (exotoxins) resemble enzymes?

Answer 9

Protein-based
Denaturable
Catalytic activity
Have a degree of specificity

Question 10

Which routes does DT use to enter host cells?

Answer 10

Direct entry and RME

Question 11

What is direct entry and which toxins use it?

Answer 11

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

Question 12

How does DT enter a host cell via RME?

Answer 12

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

Question 13

What are AB toxins and what do they do?

Answer 13

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

Question 14

What is an A+B toxin?

Answer 14

The toxin is synthesized and secreted as two independent subunits

Question 15

What is an A-B toxin?

Answer 15

Components are synthesized separately but associate during secretion

Question 16

What is a 5B toxin?

Answer 16

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

Question 17

What is a 5B toxin?

Answer 17

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

Question 18

What is an A/B toxin?

Answer 18

Components are synthesized as a single polypeptide then cleaved into subunits

Question 19

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

Answer 19

5B, RME

Question 20

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

Answer 20

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

Question 21

Which receptor that DT bind to on the host cell?

Answer 21

HP-EGF receptor (growth factor)

Question 22

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

Answer 22

disulfide bridges and they are broken by host cell receptors

Question 23

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

Answer 23

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

Question 24

What is DT encoded by?

Answer 24

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

Question 25

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

Answer 25

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

Question 26

What covalently links ADP-ribose to its target?

Answer 26

Subunit A

Question 27

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

Answer 27

Whooping cough Type IV secretion system RME or direct entry

Question 28

What type of toxin is PT?

Answer 28

An ADP-ribosylating AB5-type toxin

Question 29

What is the mode of action of PT?

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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

Answer 31

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

Question 32

What does the B subunit of PT recognize?

Answer 32

Several different targets and acts independently as a functioning toxin

Question 33

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

Answer 33

Watery discharge/diarrhea Prophage

Question 34

What do the 5B subunits associate into in CT?

Answer 34

A barrel structure that is often heavily glycosylated

Question 35

What does heavy glycosylation allow?

Answer 35

Immune evasion and increased host range

Question 36

What is CT secreted by?

Answer 36

Type II secretion system

Question 37

What else does CT secrete?

Answer 37

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

Question 38

Where does cholera colonize?

Answer 38

The small intestine

Question 39

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

Answer 39

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

Question 40

How does CT move from endosomes to the ER?

Answer 40

Via retrograde transport

Question 41

How does CT get to the cytoplasm?

Answer 41

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

Question 42

Mode of action of CT?

Answer 42

Refer to notes

Question 43

What is KDEL?

Answer 43

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

Question 44

Where is KDEL located and where does it bind?

Answer 44

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

Question 45

What does binding at the KDEL sequence cause?

Answer 45

Euk host to traffic toxin from endosomes to ER

Question 46

What are pore-forming toxins?

Answer 46

Protein exotoxins (secreted)

Question 47

What do pore-forming toxins do?

Answer 47

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

Question 48

What do PFTs insert into a host cell membrane?

Answer 48

A transmembranous pore

Question 49

What do PFTs disrupt and what are they secreted by?

Answer 49

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

Question 50

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

Answer 50

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

Question 51

What is a partially-formed pore?

Answer 51

Assembly of the PFT is simultaneous with insertion Alpha-toxin

Question 52

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

Answer 52

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

Question 53

How do partially-formed pores work?

Answer 53

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

Question 54

What happens at an active PFT?

Answer 54

Toxin accumulates and oligomerizes