Fluid Secretion Caused by Aerolysin-Like Hemolysin of Aeromonas sobria in the Intestines Is Due to Stimulation of Production of Prostaglandin E ₂ via Cyclooxygenase 2 by Intestinal Cells

Abstract

To clarify the mechanisms of diarrheal disease induced by Aeromonas sobria, we examined whether prostaglandin E 2 (PGE 2 ) was involved in the intestinal secretory action of A. sobria hemolysin by use of a mouse intestinal loop model. The amount of PGE 2 in jejunal fluid and the fluid accumulation ratio were directly related to the dose of hemolysin. The increase over time in the level of PGE 2 was similar to that of the accumulated fluid. In addition, hemolysin-induced fluid secretion and PGE 2 synthesis were inhibited by the selective cyclooxygenase 2 (COX-2) inhibitor NS-398 but not the COX-1 inhibitor SC-560. Western blot analysis revealed that hemolysin increased the COX-2 protein levels but reduced the COX-1 protein levels in mouse intestinal mucosa in vivo. These results suggest that PGE 2 functions as an important mediator of diarrhea caused by hemolysin and that PGE 2 is produced primarily through a COX-2-dependent mechanism. Subsequently, we examined the relationship between PGE 2 , cyclic AMP (cAMP), and cystic fibrosis transmembrane conductance regulator (CFTR) Cl ؊ channels in mouse intestinal mucosa exposed to hemolysin. Hemolysin increased the levels of cAMP in the intestinal mucosa. NS-398 inhibited the increase in cAMP production, but SC-560 did not. In addition, H-89, a cAMP-dependent protein kinase A (PKA) inhibitor, and glibenclamide, a CFTR inhibitor, inhibited fluid accumulation. Taken together, these results indicate that hemolysin activates PGE 2 production via COX-2 and that PGE 2 stimulates cAMP production. cAMP then activates PKA, which in turn stimulates CFTR Cl ؊ channels and finally leads to fluid accumulation in the intestines.

Microbiome patterns reveal the transmission of pathogenic bacteria in hilsa fish (Tenualosa ilisha) marketed for human consumption in Bangladesh

“…Aerolysin (aer) and haemolysin (hly) are associated with increased intestinal secretion and cause diarrhoea and gastroenteritis (Uma et al 2010). Previous research on Aeromonas hydrophila and Aeromonas sobria revealed 68Á9% of isolates to be concurrently positive for aer and hly in diarrhoea and gastroenteritis patients (Fujii et al 2008). Our study found that 90% of samples from Dhaka and 80% of samples from Chittagong were simultaneously positive for aer and hly.…”

“…Previous research on Aeromonas hydrophila and Aeromonas sobria revealed 68·9% of isolates to be concurrently positive for aer and hly in diarrhoea and gastroenteritis patients (Fujii et al . ). Our study found that 90% of samples from Dhaka and 80% of samples from Chittagong were simultaneously positive for aer and hly .…”

Short communication. Isolation of Aeromonas hydrophila in piglets

“…These bacteria possess several virulence factors (Daily et al, 1981;Fujii et al, 2008) and have been reported as responsible of septicemia in both humans (Talon et al, 1998;Janda & Abbott, 2010) and dogs (Janda & Abbott, 2010). Besides the association with the above pathological conditions, these bacteria have been isolated from feces of dogs, cats, horses, cattle, sheep and pigs, a fact explaining the ubiquity of these organisms in nature (Ghenghesh et al, 1999).…”

An aerolysin‐like enterotoxin from Vibrio splendidus may be involved in intestinal tract damage and mortalities in turbot, Scophthalmus maximus (L.), and cod, Gadus morhua L., larvae

“…Aeromonas hydrophila can cause gastroenteritis, deep wound infections and septicaemia (Buckley 1999), and Aeromonas sobria is a related species causing acute gastroenteritis in adults and children (Tanoue, Takahashi, Okamoto, Fujii, Taketani, Harada, Nakano & Nakaya 2005). Aerolysin is recognized as the major virulence factor for these organisms, and the aerolysin toxin of A. sobria has been shown to cause fluid accumulation in the mouse ileal loop test and to activate cyclic AMP (cAMP)-dependent chloride secretion (Tanoue et al 2005) via prostaglandin E2 stimulation (Fujii, Tsurumi, Sato, Takahashi & Okamoto 2008) causing diarrhoea in a manner similar to that of V. cholerae and E. coli. Thus, the mechanism by which aerolysin causes damage to cells of the gastrointestinal tract mucosa in humans and subsequent diarrhoea is well understood, and vibrioaerolysin may well have a similar, damaging effect when V. splendidus colonizes the intestinal tract of marine fish larvae in sufficient numbers.…”