Vibrio Cholerae-Cholera Toxin Flashcards
What’s this main virulence factor nonsense?
even SMALL doses of CToxin results in FULL-BLOWN diarrheas.
I dont believe you!!
You should!-mutants lacking toxin genes are considerably LESS VIRULENT
What is the toxin made up of?
- Two subunits: A and B.
- ctxA ctxB operon carried by the lysogenic CTX prophage
Tell me more about A
1 A subunit-ctxA gene product, cleaved to yield ACTIVE A1 subunit
What does A1 subunit do?
catalyzes ADP-ribosylation of the regulatory G protein (Gs-alpha)
What does the regulatory G protein, Gs-alpha, do?
modified Gs-alpha constitutively activates mammalian adenylate cyclase (AC)
What does AC (adenylate cyclase) activation lead to?
INCREASED cAMP levels
What do I do with all this extra cAMP?
cAMP activates cAMP-dependent protein kinase A (PKA)
Who does PKA hang out with?
PKA PHOSPHORYLATES proteins that are involved in intestinal ion transport (EFFLUX of ION and WATER).
Why do I care about ion transport?
- UNREGULATED ion transport causes water to leak into the intestinal lumen.
- RESULT: SEVERE, WATERY, DIARRHEA
Tell me more about B
FIVE (5) B subunits-ctxB gene product
Why do I even care about B?-Reason #1/2
Required for secretion of A1 toxin out of bacterial cell.
Why do I even care about B?-Reason #2/2
Required for interaction with host cell surface receptor, GM1 glycoprotein (GM1gpR)…leads to: A1 subunit entry into host membrane
