Lecture 13: Bacterial Toxins II Flashcards
transcriptional repression of Diptheria toxin
coupled to iron status
promotoer/operator syystem.
dtxR: repressor, is active when iron levels are high. This would indicate that iron is available and probably not in a host, not needing to translate the toxin. Iron bind the repressor, which binds the operator and prevents toxin expression.
When iron levels fall, then the repressor is rendered inactive, and the gene product can be transcribed.
Basal transcription or an activator for the promoter.
prophage-mediated regulation
vibrio-cholera
ctx is expressed on a prophage. There is a pili receptor for the ctx prophage to gain entry. Need the pili prophage first, the ctx prophage
biological program of botulinum toxin
Toxin targets and specifically enter motor neurons. neurotropic.
The toxin itself: A subunit is a protease that cleaves snare proteins.
Snare proteins are required for the release of Acetylcholine.
Snare protein can not form a tether to fuse the neurotransmitter vesicle to the nerve ending.
Leads to muscle paralysis.
Vibrio Cholera toxin, 2-stage regulation
The toxin is expressed on a pro-phage
There is a pili receptor that is expressed on another prophage.
The pili expressing prophage has to be taken up first, so it can then express the receptor for cholera bearing prophage.
This is 2 stage toxin expression.
biological program of vibrio cholera
Cholera is caused by 2 serotypes. 01 and 0139. They encode the ctx.
Very complex regulation of ctx. (6 current genes known for expression/regulation)
In vivo regulation is not fully understood.
Cholera toxin is an AB5 toxin
A subunit inserted into the center of the B subunit pentameric ring
B subunit of cholera recognizes GM1 sugar
receptor-mediated endocytosis
CTX travels via retrograde trafficking
fuses into the ER and then can be secreted
cholera toxin has ADP-ribosylation of g-protein-coupled protein for Adenylate cyclase.
Constitutive chloride efflux from cells
leads to massive cellular water loss.
Leads to diarrhea.
A-B toxins are usually taken into the cell via
Receptor-mediated endocytosis. A subunit of toxin must then exit the endosome… Lower pH, or retrograde transport via ER.
why should newborns not ingest honey
Botulinum toxin. Spore forming soil anaerobe. Can coat plants. Bees can pick up pollen and botulinum spores.
secretion of toxins, how is it done.
Dedicated toxin secretion systems
exploit common secretion mechanisms: cholera
bacterial lysis, induce cell death to release the toxin
outer membrane vesicles
Cholera use type __ secretion system
Type II secretion system
