Virulence Regulation II Flashcards
What is cholera?
Life-threatening diarrheal disease can rapidly attain epidemic proportions through inadequate sanitation
What is the cure for cholera?
Good, fresh water
Is vibrio cholerae Gram (+) or (-)?
Gram (-)
Is vibrio cholerae extracellular or intracellular?
Extracellular
How does cholera cause disease?
- be ingested
- survive passage through the gastric acid barrier of the stomach
- colonize the upper small intestine
- produce & excrete toxin
- disseminate in a watery diarrhea
What happens to the product of ctxA?
It is cleaved into A1 and A2
What happens to the product of ctxB?
Multiple B units form a coat around A1 and A2
What is the function of the A1-A2-B complex?
It binds to a receptor and delivers A1 into the host membrane
What does A1 do in the host membrane?
A1 subunit modifies (ADP-ribosylation) a G (GTP-binding) protein
What happens with the A1-modified G protein?
Modified G protein activates Adenylate cyclase continually, causing the host to continually produce cAMP
With cholera toxin causing increased cAMP production, what is the result of this?
Activation of large amounts of PKA will lead to the release of H2O and electrolytes into the intestinal lumen and lead to watery diarrhea.
How is timing of gene expression related to the toxicity of cholera?
Flagellar genes expressed when toxin genes are not so the bacteria can reach the site of colonization FIRST before they settle down.
TCP
Toxin Colonization Pilus
ACF
Accessory Colonization Factors
What is the regulation of the ToxR regulon at low temperature?
ToxR ToxS transcription is turned on at low temperature
What is the function of toxR and toxS?
They are inserted into the membrane and remain there until further stimulation
What is the regulation of the ToxR regulon at high temperature?
ToxR & ToxS proteins are no longer synthesized
What happens to the ToxR regulon when the V. cholerae reaches the lumen of the small intestine?
However once inside the host intestine an intestinal (lumenal) signal is sent to ToxR & ToxS which activates the ToxR regulon. Lumenal signal received and ToxR and ToxS will activate ToxT synthesis.
What is the auto regulatory function of the ToxT protein?
It is a transcription factor which will bind to a site near ToxR and help recruitment of RNAP and ToxT auto regulates and increases toxT transcription.
What are the other functions of ToxT?
ToxT also activates transcription of a pathogenicity island the TCP-ACF element.
ToxT also regulates transcription of the ctxA ctxB operon carried by the lysogenic CTX prophage
What is the sensor of the ToxR regulon?
ToxS
How does the intestinal signal lead to cholera pathogenicity?
It caused ToxR to bind the TCP-ACF element which leads to the transcription of toxT making ToxT protein which AUTOREGULATES its gene as well as the genes of the ct. operon that lead to ctxA and ctxB which will cause cholera.
