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Flashcards in Bacterial Toxins Deck (19)
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1
Q
  1. Define and describe microbial toxins.
A
2
Q
  1. Explain how a microbial toxin is implicated in pathogenesis of an infectious disease.
A

C. Traditional Methods to Show that a Specific Toxin Has a Role in Pathogenesis

  1. Show that purified toxin causes the same symptoms or signs as infection by the toxin-producing microbe.
  2. Show that antitoxin prevents disease caused by the toxin-producing microbe.
  3. Show that virulence of individual bacterial strains correlates with the amount of toxin that they produce.
  4. Show that non-toxinogenic mutants are avirulent, or reduced in virulence, and that virulence is restored if the microbe regains the ability to produce toxin.
3
Q

Describe the composition and properties of microbial toxins

A

1.Describe the composition and properties of microbial toxins.

Bacterial protein toxins (previously “exotoxins”)

i. usually heat-labile, immunogenic, and neutralized by specific antibodies
ii. Found outside the bacterial cell wall

directly injected into eukaryotic cells

released by lysis of bacteria

lipopolysaccharides (LPS) of Gram (-) bacteria (“endotoxin”)

i. act as a PAMP that is recognized by innate immune system, cytokine involvement
ii. :

activate macrophages, B cells, antibody production, alternative complement pathway à fever, produce acute phase reactants, polyclonal antibodies and inflammation

high LPS dose

shock and DIC

4
Q

1- Toxins that facilitate spread of microbes through tissues
breaks down ​

A

They break down extracellular matrix and degrade debris in necrotic tissue.

Examples:

  • Hyaluronidase
  • Collagenase and other proteases
  • Streptokinase
  • Deoxyribonuclease
5
Q

2- Toxins that damage cellular membranes

A

Usually kill target cells- tissue, phagocytes.

–> cytolysins, hemolysins

Pore-forming toxins

  • Assemble into multimeric complexes with hydrophobic domains that insert into membranes.
  • Create unregulated pores in the membrane of targeted cells, resulting in killing and/or lysis of target cells.

Examples:

Streptococcus pneumoniae (pneumolysin)

Group A and B streptococci (β-hemolysins)

Staphylococcus aureus (α-toxin, *Panton-Valentine leukocidin PVL)

Escherichia coli (β-hemolysin)

6
Q

2- Toxins that damage cellular membrane

The hydrolysis of phosphatidyl choline produces __________, which acttivates a variety of second messenger pathways.

A

Pore-forming toxins

**Phospholipases- degrade cell membrane phospholipids and disrupt the integrity of the membranes.

–>Bacterial phospholipase C toxins may activate second messenger pathways in addition to lysing cells:

A major component of biological membrane lipids are *phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.

The hydrolysis of phosphatidyl choline produces diacylglycerol, which activates a variety of second messenger pathways. End result is activation of arachidonic acid pathway and production of thromboxane A2…vascular permeability and edema

7
Q

Toxins that stimulate cytokine production

A

“Superantigens”

Trigger excessive and aberrant activation of T-cells

Superantigen toxins are particularly prevalent in staphs and streps. Staph aureus – 24; GAS – 11.

Also a few in coagulase negative staph and other b-hemolytic streptococci:

•Staphylococcus aureus

–>enterotoxins (emetic)

–>Enterotoxin-like (not emetic)

–>TSST-1 (Staphylococcal toxic-shock syndrome)

  • Streptococcus pyogenes
  • pyrogenic exotoxins (e.g., scarlet fever)

Streptococcal toxic-shock syndrome

8
Q

Classification of Bacterial protein toxins:

A

Toxins that inhibit protein synthesis

Inhibit protein synthesis irreversibly**

Modifying (inactivating) components of protein synthesis apparatus

Results in the death of intoxicated cells

9
Q

Diphtheria toxin

A
10
Q

How does diphtheria toxin causes disease:

A
11
Q

ADP-ribosylation in diphtheria toxic exclusive to diphtheria?

A
12
Q

Pseudomonas aeroginosa exotoxin A in comparisson to Diphtheria toxin:

A

How are they different?

13
Q

Shiga toxin of shigella dysenteriae

How does it lead to disease?

A
14
Q

Toxins that modify intracellular signaling pathways:

A
15
Q

Action of cholera toxin (LT= heat labile toxin):

A

FA:

It overactivates adenylate cyclase to increase cAMP and increase secretion of Cl- in gut followed by water efflux–> watery diarrhea

16
Q

Toxins that inhibit the release of neurotransmitters:

A
17
Q

Toxins that inhibit the release of neurotransmitters:

A
18
Q
  1. Explain the principles of immunization against toxin-mediated diseases
A
19
Q
A