A pore-forming toxin produced by Aeromonas sobria activates cAMP-dependent Cl− secretory pathways to cause diarrhea

Aeromonas sobria hemolysin (ASH) is one of the major virulence factors produced by A. sobria, a human pathogen that causes diarrhea. We investigated the effects of ASH on Cl− transport in human colonic epithelial cells. ASH increased short-circuit currents (Isc) and 125I efflux from Caco-2 cells, indicating ASH activate Cl− secretion. Additions of inhibitors of cyclic AMP dependent Cl− channels, glybenclamide and NPPB suppressed the Isc and 125I efflux increases induced by ASH. And ASH increased the intracellular cyclic AMP concentration. Moreover, ASH stimulated fluid accumulation in the iliac loop test, and glybenclamide and NPPB suppressed this fluid accumulation. Thus, cAMP-dependent Cl− secretory pathway could be related with diarrhea induced by A. sobria.