1.13. Bacterial toxins

Question 1

TOXINS:

Answer 1

Soluble substances that alter the normal metabolism of host cells with deleterious effects on the host

Question 2

TOXOIDS:

Answer 2

inactive toxins used as vaccines

Question 3

Classification according to mode of action

Answer 3

1. Damage membranes
2. Inhibit protein synthesis
3. Activate second messenger pathways
4. Activate immune response
5. Protease

Question 4

damage membranes

Answer 4

• Many exotoxins have the capacity to damage the extracellular matrix or the plasma membrane of eukaryotic cells
• Direct lysis of cells/ facilitate bacterial spread through tissues
• Enzymatic hydrolysis or pore formation

Question 5

S. aureus –alpha Toxin

Answer 5

• Oligomerizing pore-forming cytotoxin
• The a-toxin gene resides as a single copy on the chromosome of most pathogenic S. aureus strains
• Expression is environmentally regulated at the transcriptional level by the staphylococcal accessory gene regulator (agr) locus
• The toxin assembles on the plasma membrane to form a mushroom-shaped heptamer comprising three distinct domains. The capand rimare situated at the surface of the plasma membrane while the stemserves as the transmembrane channel.
• The a-toxin pore allows the influx and efflux of small molecules and ions that eventually lead to the swelling and death of nucleated cells and the osmotic lysis of erythrocytes.
• Pore formation also triggers secondary events like the release of cytokines and inflammatory mediators

Question 6

Endotoxin

source:
chemistry:
effects/toxicity/pyrogenesis (fever) :
immunogenecity:
disease examples:

Answer 6

source: Gram negative bacteria, present in LPS of the outer membrane
chemistry: Lipid portion (Lipid A) part of the LPS

effects/toxicity/pyrogenesis (fever) :Generalized/low/Yes

immunogenecity: Low

disease examples: Gram negative sepsis/meningitis

Question 7

Exotoxin

source:
chemistry:
effects/toxicity/pyrogenesis (fever) :
immunogenecity:
disease examples:

Answer 7

source: Gram positive bacteria, product of the growing bacteria
chemistry: Proteins, AB-toxins

effects/toxicity/pyrogenesis (fever) :Organ related/High/No

immunogenecity: High, can be used for vaccines, also can sometimes be neutralized by anti-toxin

disease examples: Clostridium difficile, Tetanus, Botulism, Scarlet fever

Question 8

The Rho family of GTPases

Answer 8

-small signalling G proteins
•Regulate many aspects in intracellular actin formation
•”molecular switches”
•Roles include: Organelle development,cytoskeletal dynamics, cell movement, and other common cellular functions

Question 9

Examples of bacterial toxins that activate secondary messenger pathways.

Answer 9

1) Binding of the heat-stable enterotoxins (ST) to a guanylate cyclase receptor results in an increase in cyclic GMP (cGMP) that adversely effects electrolyte flux.
2) By ADPribosylationor glucosylationrespectively, the C3 exoenzyme (C3) of Clostridium botulinum and the Clostridium difficile toxins A and B (CdA& CdB) inactivate the small Rho GTP-binding proteins.
3) Cytotoxic necrotizing factor (CNF) of E. coli and the dermonecrotic toxin (DNT) of Bordetella species activate Rho by deamidation

Question 10

Activate the immune response: conventional response

Answer 10

Presentation: Requires processing by antigen presenting cell (APC)

antigen recognition and T-cell activation: MCH-II restrictive

T-cell response: Small proportion of T-cells activated, highly regulated

Question 11

Activate the immune response: Superantigen response

Answer 11

presentation: Does not require

Antigen recognition and T-cell activation: MCH-II positive cells, but not restrictive

T-cell response: Massive T-cell activation (20-30%), associated with adverse consequences

Question 12

proteases

Answer 12

• Lethal toxins
• C. botulinum toxins –infant and foodborne botulism, found in large complexes in nature with proteins that provides protection/stability
• C. tetanus toxin (tetanospasmin) -synthesized from vegetative C. tetani(spores) in wounds, unbound