Inhibitory effects of 6-(phenylsulfonyl)nicotinonitrile against Vibrio vulnificus infection to host (56.16)

Abstract

Abstract Vibrio vulnificus is a gram-negative bacterium that is present in marine environment, and infection of the bacteria shows rapid pathological progress. V. vulnificus induces the fever, septic shock, the formation of secondary lesions, accompanied in many cases by ulcer and edema on the patients. Mortality of primary septicemia exceeds 50 % in septic patients. In this study, we examined the antimicrobial activity of 6-(phenylsulfonyl)nicotinonitrile, named U262, against V. vulnificus in vitro and in vivo. Treatment with U262 significantly inhibited the V. vulnificus-induced cytotoxicity in human intestinal epithelial INT-407 cells. U262 itself was not toxic to host cells, and did not affect the growth of the bacteria. Interestingly, U262 treatment significantly decreased the attachment of V. vulnificus to the INT-407 cells. Furthermore, the administration of U262 increased the survival period of V. vulnificus-infected mice. The numbers of viable V. vulnificus in the small intestine, liver, spleen and blood were significantly lower in the U262-treated mice, compared with those of the untreated mice. Taken together, these results demonstrate that U262 suppresses the V. vulnificus-mediated cytotoxicity in human intestinal epithelial cells, maybe via the down-regulation of bacterial attachment to the epithelial cells, and suggest that U262 can be utilized as a novel candidate in the treatment of V. vulnificus infection.