Development of new biosensors to detect ciguatoxins
Résumé
Ciguatoxins are lipid-soluble polyether compounds produced by dinoflagellates from the genus Gambierdiscus spp.. Ciguatoxins are mostly found in tropical and subtropical zones; however, within the last decade, they have been identified in fishes caught in European waters, notably in Madeira (1) and Canary Islands (2), while Gambierdiscus spp. have also been found both in the NE Atlantic Ocean (3) and in the Mediterranean Sea (4). These toxins bind to Voltage Gated Sodium Channels at the surface of human sensory neurons where they remain, causing Ciguatera Fish Poisoning with a variety of gastrointestinal, cardiovascular and neurological symptoms (paresthesia, ataxia, cold allodynia), including persistent neurological effects. Ciguatera is the major cause of food poisonings by seafood worldwide, with an estimated 50 000 to 500 000 victims per year. However, there is so far no simple and quick way of detecting these toxins in contaminated samples. Currently, only heavy and expensive laboratory methods are available to detect them: LC-MS/MS, receptor-binding assays by competition with radiolabeled compounds, and neuroblastoma cell-based assays performed on mammalian neurons (5). We have started to engineer biosensors based on the detection of a transcriptional signal in the yeast model Saccharomyces cerevisiae. This unicellular eukaryotic model is well-known and easy to genetically modify, grows fast and presents a very good conservation of signaling pathways with higher eukaryotes. We present a series of genetically modified yeast strains which allow us to follow the activation of specific signaling pathways responding linearly to ciguatoxin exposure.
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