Bacterial toxins

Question 1

Toxins that break ECM/cellular junctions - example

Answer 1

Proteases.

Eg Bacteroides fragilis enterotoxin > cleaves E-cadherin > loss of aj

Question 2

Modes of action of toxins that attack lipid bilayer (cytolysins)

Answer 2

1. Enzymatic activity (phospholipases, licithinases)

2. Physical acitvity (small and large pore forming toxins)

Question 3

RTX toxins

Answer 3

Repeats-in-toxins (Ca2+ binding site).
Extracellular secretion by T1SS.
Pore-formation.

Question 4

Perfringolysin

Answer 4

Secreted by Clostridium perfringens.

Receptor: cholesterol > oligomerization > pore formation

Question 5

Cytolysins

Answer 5

Secreted, toxic to specific cells causing lysis.
Pore formation >leakage > matbolic disruption > lysis.

Hemolysins target erys.

Question 6

Toxins that act inside cells

Answer 6

AB toxins
Self-transporters
Injected (T3/4SS)

Question 7

AB toxin types

Answer 7

Inhibit protein synthesis (eg Diphteria toxin)

Protease activity (eg Tetanus toxin)

Question 8

Diphteria toxin

Answer 8

Bacterial ADP-ribosyltransferase.
AB toxin.
Receptor: B chain of EGF

B binds receptor > endocytosis > acidification in endosome > translocation of A into cytosol > A ADP-ribosylates host EF-2 inhibiting translation > cell death

Question 9

Pseudomonas exotoxin A

Answer 9

Similar to DT.

ADP-ribosylation of EF2.

Question 10

Tetanus toxin

Answer 10

Acts on motoinhibitory neurons: targets SNARE proteins > inhibits release of GABA and glycin > continuour motoneuron activity > spastic paralysis

Transmission via wounds.

Question 11

Botulinum toxin

Answer 11

Acts on motoneurons > cleaves SNARE proteins (mediate vesicle fusion) > acetlcholine vesicles cannot bind to intracellular membrane, release inhibited > loss of motoneuron activity > flaccid paralysis

Toxins in contaminated food.

Question 12

Toxins affecting signal transduction - example

Answer 12

Cholera toxin.

Subunit B binds > subunit A ADP-ribosylates G-alpha protein > maintained in active state > increased adenylate cyclase activity > increased intracellular cAMP conc > overactivation of PKA > CFTR phosphorylation > eelctrolate and water efflux into intestinal lumen > watery diarrhea

Question 13

Toxicity via inflammation

Answer 13

Superantigens,
endotoxins (LPS),
chronic stimulation

Question 14

Superantigens

Answer 14

No ag processing, direct binding to MHCII and TCR, oligoclonal T cell activation > massive cytokine release, unspecific immune response

Eg TSST-1, staphylococcal enterotoxin B