Vibrio Cholerae Virulency

• Cholera is not an invasive infection
• Organisms do not reach blood, only act locally
• Cholrae attach to the jejunal epithelial cell by special fimbria .
• They multiply and liberate cholera toxin and perhaps Mucinase and Endotoxin.
• Pathogencity of 0-139 vibrio is due to 0 antigen
• Any medication or conditions that decreases stomach acidity makes a person more susceptible to infection with V.cholrae

TOXINS OF VIBRIO CHOLERA:

ENTEROTOXIN(CTX/CT/Choleragen/Permeability factor)

• Produce heat labile enterotoxin.
• The genes for enterotoxin are on part of genome of bacteriophage.
• CT demonstrated by Skin blueing test.
• Toxin production is determined by a filamentous phage integrated with bacterial chromosome.
• It is antigenically related to heat labile toxin of Escherichia

MECHANISM OF ACTION:

• Cholera toxin consists of 2 subunits

1. Monomeric enzymatic moiety (A subunit):Further divided  A₁ and A₂
2. Pentameric binding moiety (B subunit)

• Ganglioside GM1 serves as a mucosal receptor for subunit B
• It promotes entry of subunit A into the cell
  • Activation of subunit A₁ which interacts with cytosolic proteins called ADP-ribosylation factors (ARF)
  • ARF-A1 complexes catalyze ADP-ribosylation of a G-protein called GSa.
  • ADP-ribosylated Gsa in turn binds to and stimulates adenylate cyclase 
  • This causes increased levels of intracellular cAMP 
  • cAMP inhibits the absorptive sodium transport system
  • Activates the secretory chloride transport system
  • Results in prolonged hyper secretion  of water and electrolytes
  • Na⁺ and Cl^– absorbtion dec.
  • Inc. secretion of K+ and HCO₃ 
  • Therefore isotonic diarrhea,acidosis with elevated anion gap(inc serum lactate protien)
  • No effect on other tissue
  • Intestinal secretion also increased by PG and Neural histamine receptors