pathogenesis of cholera

pathogenesis of cholera

1. large infective dose required

   • 10 to hower 9 - 10 to power 11 organisms
     • this many needed as majority are killed by acidity

2. colonisation of small intestine is dependant on

   • motility of organism: non motile mutants are less virulent
   • production of mucinase aka protease
     • this allows bacterium to penetrate mucosal layer and adhere to receptors on epithelial cells
     • once adhered to epithelial cell receptors they release entertain known as cholera toxin
   • adhesion
     • due to TVP: toxin co regulatory pilus

3. symptoms mainly due to cholera toxin

   • cholera toxin
     • AB subunit toxin
       • B binds to receptor on epithelial cells
         • this allows A to translocate to cytoplasm
           • neuraminidase cleaves siallic acid to make it more like GM1 and create more receptors
             • Target protein is regulatory G protein Gs that activates host cell adenylate cyclase giving high levels of cAMP from ATP, The cAMP is an intracellular signal to cause active secretion from epithelial cells of Cl- and HCO3- ions, decreased absorption of Na+ and Cl- and results in a massive loss of water and electrolytes from body (diarrhoea). [The synthesis of cholera toxin is regulated by a gene toxR which in turn is influenced by environmental signals, including pH, osmolarity, and temperature.]

4. the organism sits on surface of all intestine

5. additional toxins

   • effects intracellular tight junctions
     • increases permeability of small intestine mucosa
   • Ace: accessory cholera toxin