Mechanisms underlying V. cholerae-induced diarrhea. Cholera is characterized by severe watery diarrhea due to changes in ion secretion and absorption. Both CLCA and CFTR-dependent Cl− secretion are activated, the first by Ace and the second by cholera toxin and NAG heat-stabile toxin. Increased cAMP levels also block sodium absorption through NHE2 and NHE3. V. cholerae also creates anion permeable pores through insertion of VCC. In concert with changes in ion transport, paracellular permeability is also decreased. Zot interaction with zonulin causes ZO-1 to dissociate from tight junctions while HA/P cleaves occludin and rTX interferes with the contractile actin ring.