Steps of cholera - Intro to cell biology & genetics

Step 1

Vibrio swim to brush border cells

Step 2

Vibrio attaches using pili to a glycolipid

Step 3

Vibrio release cholera toxin (CT) and Zot1

Step 4

CT binds to ganglioside receptor and Zot1 disrupts tight junctions

Step 5

Ganglioside receptor taken into the cell through endocytosis. Vesicle goes to lysosome. Lysosome releases piece of cholera toxin

Step 6

B-adrenergic receptor activates G-protein on basal side of membrane by GTP Exchange Factor (GEF) and replaces GDP with GTP

Step 7

G-protein activates adenylyl cyclase which produces the second messenger cAMP

Step 8

cAMP diffuses across the cell and activates Protein Kinase A (PKA)

Step 9

PKA phosphorylates CFTR and thereby activates it

Step 10

CFTR releases Cl- into lumen of small intestine which disrupts the electrochemical gradient and osmolarity

Step 11

Na+ and water flow out in between brush border cells because Zot1 has disrupted the tight junctions

Step 12

K+ and Na+ pulled out of brush border cells by disruption in electrochemical gradient increasing osmolarity gradient

Step 13

Water leaves brush border cells via osmosis through aquaporin (osmosis) and in between cells because tight junctions are disrupted

Step 14

Water and electrolytes in the interstitial space are lost by being pulled into brush border cells or by leaking in between cells

Step 15

Water and electrolytes are replenished from blood sera causing hypovolemic shock. The capillaries that line the small intestine are fenestrated capillaries meaning they have pores that allow molecules and atoms to diffuse across

Step 16

Bicarbonate (HCO3-) is pulled from blood into brush border cells and flow out through CFTR

Step 17

Metabolic acidosis results (drops in blood pH) which accelerates kidney failure (i.e. renal failure)

Step 18

Organ failure ensues driven by hypovolemic shock that is exacerbated by metabolic acidosis