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Flashcards in VirGeneReg2 Deck (8)
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1

What is the causative agent in cholera?

-vibrio cholerae
-extracellular pathogen
-highly motile, uni-flagellated and gram negative curved rod

2

How does v. cholerae cause disease?

-ingested
-survive passage through gastric acid of stomach
-colonize in the upper small intestine
-produce and excrete exotoxin
-disseminate in a watery diarrhea

3

What is the main virulence factor of cholera?

cholera toxin

4

How does the cholera toxin on the CTX phage work?

1. CtxA and CtxB
2. B coats A and cleaves it to A1 and A2
3. binds host GM1 receptor and A1 subunit enters host membrane
4. A1 subunit modifies ADP-ribosylation a GTP binding protein
5. modified G-protein activates adenylate cyclase
6. cAMP activates PKA
7. PKA activates transporters causing efflux of ions and water ie. diarrhea

5

Are motility genes on during colonization?

no only on to reach site of colonization and then toxigenic genes turned on

6

What is TCP? What is ACF?

toxin colonizing pilus
accessory colonizing factors

-mutations to tcp or acf reduce colonization
-located on large pathogenicity island called TCP-ACF element

7

Activation of what regulon permits the synthesis of virulence factors?

ToxR

-ToxR is the regulator

8

What are the steps of the virulence factor formation?

1. toxR and toxS transcription is turned on at low temperature (synthesized outside the body) and inserted into the membrane

2. ingested-ToxR and ToxS transcription turned off at high temp-ToxR and ToxS proteins no longer synthesized

3. once inside intestinal lumen signal is sent to ToxR and ToxS which activates ToxR regulon

4. Activates ToxT synthesis

5. ToxT autoregulates -increases ToxT transcription ---lots of ToxT synthesized

6. ToxT also activates transcription of the pathogenicity island the TCP-ACF element

7. ToxT also regulates transcription of the ctxA and ctxB operon carried by the lysogenic CTX prophage

Note: ToxT is a member of the ToxR regulon but itself is also a regulator that activates many ToxR regulon promoters

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