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 μM), 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 (20 mg/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.