Bacterial Toxins

Question 1

What are the four types of exotoxins?

Answer 1

1. Membrane-damaging toxins
2. Intracellular toxins
3. Toxins that act from the cell surface
4. Toxins that interfere with immune response

Question 2

What are exotoxins?

Answer 2

Toxin secreted by a bacteria, soluble.

Question 3

What are the 8 subtypes of exotoxins?

Answer 3

1. Membrane-damaging toxins
   - pore-forming toxins
   - toxins that enzymatically damage the membrane
   - toxins with a detergent-like effect
2. Intracellular toxins
   - AB toxins
   - Injected toxins (type III and type IV secretion)
3. Toxins that act from the cell surface
   - superantigens
4. Toxins that interfere with the immune response
   - complement inhibitors, Ig-proteases

Question 4

What are pore-forming toxins used for?

Answer 4

Gaining nutrients from cells (e.g. Fe from erythrocytes)
Spreading through tissues
Immune evasion
To escape phagosomes

Question 5

What are some characteristics of cholesterol-dependent cytolysins?

Answer 5

They are secreted as monomers by some Gram-positives.
They are inserted as a pre-pore complex
They make large pores (30-50 subunits)
They are made of alpha-helices in soluble form
Examples are : Pneumolysin (S. pneumoniae) Listeriolysin (L. monocytogenes) Perfringolysin (C. perfringens)

Question 6

What is an example of a cytolysin with enzymatic activity?

Answer 6

Clostridium perfringens alpha toxin

Question 7

What occurs with cytolysins possessing enzymatic activity at low concentrations?

Answer 7

Limited hydrolysis of phosphotidylcholine (PC)
Generation of DAG
Signal transduction pathways

Question 8

What occurs with cytolysins possessing enzymatic activity at high concentrations?

Answer 8

Massive degradation of PC

Membrane disruption, cell lysis

Question 9

What do the A and B parts of AB toxins do?

Answer 9

A - enzymatic

B - binds receptor

Question 10

How are AB toxins taken into the cell?

Answer 10

B binds receptor
Endocytosis of some form
Endosome is acidified. At this point sometimes A can escape. (Diphtheria toxin, Clostridial neurotoxins, Anthrax)
Some passed onto Golgi as part of the ER-associated degradation route (ERAD)
Passed onto the ER. Here the protein is denatured and inactivated before being released into the cytoplasm. To regain function they are modified or re-folded. (Shiga toxin, Cholera toxin, Pertussis toxin, Pseudomonas exotoxin A)

Question 11

What is the pathological effect of Cholera toxin?

Answer 11

Produced by Vibrio cholerae that carries a lysogenic phage.
After going through ER and being reactivated, the toxin catalyses the ADP-ribosylation of Gs alpha subunit, causing it to lose the ability to inactivate itself, leading to longer period of activation.
This increases levels of cAMP, which activates PKA.
PKA phosphorylates CFTR and causes active Cl secretion.
Massive efflux of electrolytes and fluids, causing excessive diarrhoea.

Question 12

How is Salmonella typhymurium taken up by the cell?

Answer 12

Recruits effector proteins to cause a ruffling of the membrane which allows the bacterium to be taken up into a vacuole.
SipA - ‘molecular staple’
SipC - directly interacts with actin
SopE - mimics GEF which is a nucleotide exchange factor.
SopB - inositolphosphatase => increase PIP which has similar effect to SopE

Question 13

Which four genera have strains possessing superantigens?

Answer 13

Staph - specifically aureus
Strep - specifically pyogense, disgalactiae, agalactiae
Yersinia - specifically pseudotuberculosis
Mycoplasma - specifically arthritidis