Bacterial Toxins Flashcards
- Define and describe microbial toxins.
- Explain how a microbial toxin is implicated in pathogenesis of an infectious disease.
C. Traditional Methods to Show that a Specific Toxin Has a Role in Pathogenesis
- Show that purified toxin causes the same symptoms or signs as infection by the toxin-producing microbe.
- Show that antitoxin prevents disease caused by the toxin-producing microbe.
- Show that virulence of individual bacterial strains correlates with the amount of toxin that they produce.
- 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.
Describe the composition and properties of microbial toxins
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
1- Toxins that facilitate spread of microbes through tissues
breaks down
They break down extracellular matrix and degrade debris in necrotic tissue.
Examples:
- Hyaluronidase
- Collagenase and other proteases
- Streptokinase
- Deoxyribonuclease
2- Toxins that damage cellular membranes
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)
2- Toxins that damage cellular membrane
The hydrolysis of phosphatidyl choline produces __________, which acttivates a variety of second messenger pathways.
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
Toxins that stimulate cytokine production
“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
Classification of Bacterial protein toxins:
Toxins that inhibit protein synthesis
Inhibit protein synthesis irreversibly**
Modifying (inactivating) components of protein synthesis apparatus
Results in the death of intoxicated cells
Diphtheria toxin
How does diphtheria toxin causes disease:
ADP-ribosylation in diphtheria toxic exclusive to diphtheria?
Pseudomonas aeroginosa exotoxin A in comparisson to Diphtheria toxin:
How are they different?
Shiga toxin of shigella dysenteriae
How does it lead to disease?
Toxins that modify intracellular signaling pathways:
Action of cholera toxin (LT= heat labile toxin):
FA:
It overactivates adenylate cyclase to increase cAMP and increase secretion of Cl- in gut followed by water efflux–> watery diarrhea
Toxins that inhibit the release of neurotransmitters:
Toxins that inhibit the release of neurotransmitters:
- Explain the principles of immunization against toxin-mediated diseases
