Microbial toxins

Question 1

6 mechanisms of action for microbial toxins

Answer 1

1. Toxins that facilitate spread of microbes through tissues
   
   2. Toxins that damage cellular membranes
   3. Toxins that stimulate cytokine production
   4. Toxins that inhibit protein synthesis
   5. Toxins that modify intracellular signaling pathways
   6. Toxins that inhibit the release of NT

Question 2

How do toxins damage cellular membranes?

Answer 2

i. Most kill target cells by forming pores / disrupting membrane integrity
ii. Many are called hemolysins because they damage erythrocytes
iii. If they also damage other cells they are called cytolysins

Question 3

How do toxins that stimulate cytokine production cause harm?

Answer 3

Streptococcus pyogenes and Staphylococcus aureus produce pyrogenic exotoxins → bind both MHC Class II and to specific V-beta chains on T-cells. → Activates T-cells→ TONS of cytokines → DAMAGE

Question 4

Why are Toxins that inhibit protein synthesis bad for us? Example

Answer 4

can irreversibly cause death of hosts

i. Diphtheria toxin and Pseudomonas aeruginosa inactivate EF-2

Question 5

Heat-labile enterotoxins (LTs) of Vibrio cholerae and E. coli

Answer 5

1) increase cAMP 2) Activate α-subunit of stimulatory Gs protein
3) Increased intracellular cAMP causes active Cl- secretion and results in diarrhea

Question 6

Heat-stable enterotoxin I (ST-I) of E. coli

Answer 6

1) Activates cGMP

2) Increased intracellular cGMP causes secretory diarrhea

Question 7

Anthrax edema factor (EF) from bacillus anthracis & adenylate cyclase toxin from Bordetella pertussis:

Answer 7

1) Adenylate cyclases that increase cAMP
2) Require activation by calmodulin and calcium - provided by target cells
3) Targets cardiomyocytes and smooth muscle/endothelial cells for lethal effects

Question 8

Explain the principles for developing novel therapeutic agents based on toxins

Answer 8

Immunotoxins & hormonotoxins - hybrid molecules

○ Lack the receptor-binding domain of the native toxin
○ Use the “A” (active) part of the toxin by coupling it to an Ab that is specific to the cell you want to destroy. –> The toxin can kill specific cells for you now (won’t kill cells without the tumor-specific receptor)

Question 9

Stage 1 bacterial cell wall synthesis inhibitors

Answer 9

Affects Synthesis and assembly of cell wall subunits occurring in the cytosol

Question 10

Stage 2 bacterial cell wall synthesis inhibitors

Answer 10

Affects Linear polymerization of subunits occurring at cell membrane

ie: vancomycin

Question 11

Stage 3 bacterial cell wall synthesis inhibitors

Answer 11

affects Cross-linking of peptidoglycan polymers occurring at the cell wall