VirGeneReg2 Flashcards
1
Q
What is the causative agent in cholera?
A
- vibrio cholerae
- extracellular pathogen
- highly motile, uni-flagellated and gram negative curved rod
2
Q
How does v. cholerae cause disease?
A
- ingested
- survive passage through gastric acid of stomach
- colonize in the upper small intestine
- produce and excrete exotoxin
- disseminate in a watery diarrhea
3
Q
What is the main virulence factor of cholera?
A
cholera toxin
4
Q
How does the cholera toxin on the CTX phage work?
A
- CtxA and CtxB
- B coats A and cleaves it to A1 and A2
- binds host GM1 receptor and A1 subunit enters host membrane
- A1 subunit modifies ADP-ribosylation a GTP binding protein
- modified G-protein activates adenylate cyclase
- cAMP activates PKA
- PKA activates transporters causing efflux of ions and water ie. diarrhea
5
Q
Are motility genes on during colonization?
A
no only on to reach site of colonization and then toxigenic genes turned on
6
Q
What is TCP? What is ACF?
A
toxin colonizing pilus
accessory colonizing factors
- mutations to tcp or acf reduce colonization
- located on large pathogenicity island called TCP-ACF element
7
Q
Activation of what regulon permits the synthesis of virulence factors?
A
ToxR
-ToxR is the regulator
8
Q
What are the steps of the virulence factor formation?
A
- toxR and toxS transcription is turned on at low temperature (synthesized outside the body) and inserted into the membrane
- ingested-ToxR and ToxS transcription turned off at high temp-ToxR and ToxS proteins no longer synthesized
- once inside intestinal lumen signal is sent to ToxR and ToxS which activates ToxR regulon
- Activates ToxT synthesis
- ToxT autoregulates -increases ToxT transcription —lots of ToxT synthesized
- ToxT also activates transcription of the pathogenicity island the TCP-ACF element
- 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
