cholera and virulence Flashcards
how does Vibrio cholerae change when in a host
it is virulent in the host but represses virulence genes when in open water and is metabolically adaptive
how does cholera control its gene expression
NOT by a two- component system, although a similar mechanism involving ToxRS and TcpPH
how does cholera cause disease
it is taken in and then produces AB toxin. this changes water-ion homeostasis and causes huge water loss and death by dehydration
how is homeostasis altered by cholera
it prevents Na+ influx into the blood. this is compensated by increasing Cl- efflux. with this, water is pumped into the gut to try to regain equilibrium
what are the virulence factors of cholera and what are their functions
flagella (to swim), ACFs (short distance adhesion) and TCP pilli bundles (long distance adhesion)
what encodes toxAB and what is its structure
it is encoded by ctxA and ctxB genes. it has 5 B subunits which form a hydrophobic ring around one pre-A subunit
how is toxAB activated
it is endocytosed and the ER cleaves pre-A into active A1. this alters G proteins to constantly bind GTP, causing production of cAMP and phosphorylation of Na+ and Cl- which alters ion movement
what is the role of AphAB
they are activated in the gut when they sense low O2 and pH and they activate transcription of TcpPH by recruiting RNAP to tcp operon
what is the role of ToxT
it is activated by both ToxRS and TcpPH and activates transcription of ctxAB, ACF and tcp genes. it diffuses to amplify regulation
how is ToxT promoted
by ToxRS and TcpPH working together. Tox/TcpP dimerise on the ToxT promoter and bind ToxS/TcpH via Cys interactions
how is coregulation of ToxT enabled
ToxRS binds promoter first, displacing His and bringing TcpPH closer to its promoter to enable binding. TcpPH binding is what recruits RNAP
why are bile salts important
they allow TcpP to dimerise. they also enable ToxRS to directly regulate genes
what is the difference between ToxRS and ToxT regulation
ToxRS directly regulates ancestral genes whereas ToxT regulates more modern genes which may not have been present in primitive cells eg tcp pillu, strong adhesion factors (before evolution of peristalsis) etc
how does ToxT regulate genes
via AT rich ‘toxboxes’ which recruit the alpha CTD of RNAP
how does ToxT self- regulate
the ToxT protein product binds to and activates the TcpA operon promoter, upstream of the ToxT operon
