Virulence Regulation II

Question 1

What is cholera?

Answer 1

Life-threatening diarrheal disease can rapidly attain epidemic proportions through inadequate sanitation

Question 2

What is the cure for cholera?

Answer 2

Good, fresh water

Question 3

Is vibrio cholerae Gram (+) or (-)?

Answer 3

Gram (-)

Question 4

Is vibrio cholerae extracellular or intracellular?

Answer 4

Extracellular

Question 5

How does cholera cause disease?

Answer 5

• 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

Question 6

What happens to the product of ctxA?

Answer 6

It is cleaved into A1 and A2

Question 7

What happens to the product of ctxB?

Answer 7

Multiple B units form a coat around A1 and A2

Question 8

What is the function of the A1-A2-B complex?

Answer 8

It binds to a receptor and delivers A1 into the host membrane

Question 9

What does A1 do in the host membrane?

Answer 9

A1 subunit modifies (ADP-ribosylation) a G (GTP-binding) protein

Question 10

What happens with the A1-modified G protein?

Answer 10

Modified G protein activates Adenylate cyclase continually, causing the host to continually produce cAMP

Question 11

With cholera toxin causing increased cAMP production, what is the result of this?

Answer 11

Activation of large amounts of PKA will lead to the release of H2O and electrolytes into the intestinal lumen and lead to watery diarrhea.

Question 12

How is timing of gene expression related to the toxicity of cholera?

Answer 12

Flagellar genes expressed when toxin genes are not so the bacteria can reach the site of colonization FIRST before they settle down.

Question 13

TCP

Answer 13

Toxin Colonization Pilus

Question 14

ACF

Answer 14

Accessory Colonization Factors

Question 15

What is the regulation of the ToxR regulon at low temperature?

Answer 15

ToxR ToxS transcription is turned on at low temperature

Question 16

What is the function of toxR and toxS?

Answer 16

They are inserted into the membrane and remain there until further stimulation

Question 17

What is the regulation of the ToxR regulon at high temperature?

Answer 17

ToxR & ToxS proteins are no longer synthesized

Question 18

What happens to the ToxR regulon when the V. cholerae reaches the lumen of the small intestine?

Answer 18

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.

Question 19

What is the auto regulatory function of the ToxT protein?

Answer 19

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.

Question 20

What are the other functions of ToxT?

Answer 20

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

Question 21

What is the sensor of the ToxR regulon?

Answer 21

ToxS

Question 22

How does the intestinal signal lead to cholera pathogenicity?

Answer 22

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.