Protective mechanism of curcumin against Vibrio vulnificus infection.

Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., has many beneficial biological activities. However, there are relatively few reports of the effects of curcumin on pathogen infections. This study examined the effect of curcumin on a Vibrio vulnificus infection. The cytotoxicity of V. vulnificus to HeLa cells was significantly inhibited by curcumin (at 10 or 30 µM). To further examine the inhibitory mechanism of curcumin against V. vulnificus-mediated cytotoxicity, the level of bacterial growth, bacterial motility, cell adhesion, RTX toxin expression and host cell reactions were evaluated. Curcumin inhibited V. vulnificus growth in HI broth. Curcumin inhibited both bacterial adhesion and RTX toxin binding to the host cells, which can be considered the major protective mechanisms for the decrease in V. vulnificus cytotoxicity. Curcumin also inhibited host cell rounding and actin aggregation, which are the early features of cell death caused by V. vulnificus. In addition, curcumin decreased the V. vulnificus-induced NF-κB translocation in HeLa cells. Finally, curcumin protected mice from V. vulnificus-induced septicemia. In conclusion, curcumin may be an alternative antimicrobial agent against fatal bacterial infections.

Resveratrol modulates RTX toxin-induced cytotoxicity through interference in adhesion and toxin production.

Host-parasite contact is a prerequisite for the acute cytotoxicity of Vibrio vulnificus, which is mediated primarily by RtxA1, a repeat in toxin (RTX) toxin. We found that resveratrol (at 10 or 30 microM), a natural polyphenol, protected HeLa cells from V. vulnificus cytotoxicity. To further characterize the underlying mechanism, the effect of resveratrol was investigated at the level of the host-microbe interactions. We studied the effects of resveratrol on adhesion, motility, cytotoxicity, and RtxA1 toxin expression of V. vulnificus. In addition, the effect of resveratrol on mouse mortality caused by V. vulnificus was investigated. Resveratrol inhibited V. vulnificus motility and the microbe adhesion to host cells, critical virulence traits for many bacteria. Resveratrol also down-regulated the expression of RtxA1 toxin at the transcriptional level and thereby protected the host cells from becoming rounded and damaged. In addition, resveratrol (20mg/kg) protected CD-1 mice from V. vulnificus infection. Taken together, these results suggest that resveratrol, a modulator of host-microbe interactions, has potential for development as a new paradigm drug to treat infectious diseases.