Lecture 3 - Toxins Flashcards
Name the steps required for a bacterium to cause disease.
- Encounter/enter the host
- Establish an infectious niche
- Multiply, cause tissue damage
- Spread to other tissues, other hosts, or both
Name the factors responsible for pathogenicity.
- Colonization factors (eg. allow for attachment)
- Survival factors
- Factors that cause damage or spread
- Regulatory factors
Name three purposes of toxins.
- Obtain cell-associated nutrients
- Facilitate dissemination (eg. get from epithelium to blood)
- Interfere with host defenses
Compare endotoxin vs. exotoxin
- Endotoxin is the outer membrane of the outer leaflet of Gram negative bacteria (the LPS coat).
- Exotoxin is the “classical” protein toxin synthesized by some bacteria.
How does C. dificile toxin enter a host cell?
The toxin binds to a host cell receptor, and is taken in via RME. The vesicle containing the toxin begins to acidify, which changes the toxin’s conformation to expose the hydrophobic region of the toxin. The toxin hydrophobic region enters into the membrane of the endosome which exposes the N-terminus enzymatic domain into the cytosol, and the cysteine protease domain on the toxin auto-cleaves the active domain, releasing it into the cytosol.
What type of paralysis does botulism cause?
Flaccid (think botox)
What does the “B” domain of an A-B model toxin do?
It is the cell Binding region (it binds to a cell receptor).
For an A-B toxin, what happens upon acidification of the toxin-containing endosome?
Acidification results in pore formation, which allows for toxin insertion into the endosome membrane and cleavage of the active domain into the cytosol.
What does the “A” domain of an A-B model toxin do?
The enzymatically Active domain.
Which neurotransmitters are inhibited by botulinum toxin? Where are these neurotransmitters located?
The botulinum toxin protease cleaves proteins involved in the release of stimulatory neurotransmitters such as Ach in the peripheral nerves.
Which neurotransmitters are inhibited by tetanus toxin? Where are these neurotransmitters located?
The tetanus toxin protease cleaves proteins involved in the release of inhibitory neurotransmitters such as GABA in the CNS.
What type of paralysis does tetanus cause?
Spastic paralysis.
Is cholera invasive or non-invasive?
Non-invasive (it does not invade cells in the GI tract)
What is the site of damage by cholera toxin?
Small intestine.
What is the mechanism of action of the cholera toxin?
Cholera toxin is an ADP ribosylating toxin that acts on G proteins in the intestinal epithelium. It keeps these G proteins bound to GTP, activating a cyclase -> cAMP -> decreased Na+ absorption, increased Cl- secretion, decreased H2O absorption and increased H2O secretion into the lumen.
