Abstracts from 21st Meeting of the French Society of Toxinology (SFET) / Toxicon 91 (2014) 164e184166

i IFREMER, Unit�e Dyneco (Laboratoire Pelagos), ZI de la Pointe du Diable - CS10070 - 29280 Plouzan�e, Francej Anses, Direction d’Evaluation du Risque, 94701 Maison-Alfort, France

Marine and coastal ecosystems suffer environmentalchanges linked to anthropogenic activities and climatechange. The phytoplankton compartment is at the centre ofthese ecosystems. Through its dynamic character, thiscompartment rapidly absorbs impacts and translates theminto successive cascades along the entire trophic web (bothpelagic and benthic compartments). Major changes includethe general increase in phytoplankton biomass linked toeutrophication of coastal ecosystems, changes in planktoncommunity structure and increased occurrence of harmfulalgal blooms (HABs). The term HAB comprises all phe-nomena linked to the development of microalgae whichhave direct or indirect negative effects on man: (i) theaccumulation of phycotoxins in seafood destined forhuman consumption, (ii) massive mortalities of naturalpopulations or cultivated marine organisms (through ich-tyotoxins or anoxic episodes), (iii) production of toxicaerosols causing cutaneous or respiratory irritations, (iv)reduction in tourism in affected coastal areas followingmassive proliferation of microalgae. French research isalready present in many of these domains, and is recog-nized at international level through a number of collabo-rations. However, the research teams in France aredispersed and a federation of efforts is desirable, as it willallow for an increased impact of the existing competences.Therefore, the creation of a Research Network (Groupe-ment de Recherche) has been jointly proposed by IFREMERand the CNRS, with approval in principle under the title:PHYCOTOX - from microalgae to risks for man and theecosystem. This research network has an interdisciplinaryapproach to address three societal challenges: (i) increasedcomprehension of sanitary risks posed by microalgae, (ii)evaluate the impact of HABs on the marine ecosystem and(iii) quantify socio-economic risks. The networking activ-ities will encourage research actions on the followingthemes:

1. Identification and characterisation of algal toxins2. Ecology, diversity and physiology of HAB organisms

and implications for their toxin production3. Transfer of algal toxins along foodwebs and impact on

marine ecosystems4. Sanitary impacts and quantitative risk assessment5. Socio-economic impactsLaboratoires already committed to this network include those from

the following institutions: IFREMER, CNRS, Institut Louis Malard�e and anumber of universities (Bordeaux, Bretagne Occidentale, Caen, Mont-pellier, Nantes and Pierre-et-Marie-Curie).

http://dx.doi.org/10.1016/j.toxicon.2014.08.012

5. All paths lead to Rome: Evolutionary convergence anddivergence of K+ channel blocking toxins

R.C. Rodríguez de la Vega a, T. Giraud a, b

a Laboratoire d'Ecologie, Syst�ematique et Evolution, Universit�e Paris-Sud,91405 Orsay, Franceb CNRS, UMR8079, 91405 Orsay, France

Potassium channels are key players in a number ofphysiological processes, no wonder then that venomsfrom cone snails, scorpions, sea anemones, snakes andspiders are all known to be rich sources of Kþ channelsmodulators. Most of these toxins exert their function viaa common molecular mechanism that involves theblockade of ion conduction by direct binding onto theexternal mouth of Kþ channels, leading to an abnormalcellular depolarization. Most Kþ channel blocking toxinscharacterised to date belong to one of four protein fam-ilies: i) CSab motif containing proteins, ii) the ICK fold, iii)the Kunitz-type protease inhibitors and iv) the CRISPs.While each of these toxin types are represented by largefamilies that arose through extensive gene duplicationsand resulted in a diversity of structural forms (diver-gence), the “pharmacophores”, i.e. the molecular de-terminants of Kþ channel blockade, in these structurallyunrelated types are common to all (convergence). Inorder to better understand these contrasting evolu-tionary mechanisms, we reconstructed the evolutionaryhistories of all four Kþ channel blocking toxin types andevaluated the nature of selection sculpting their molec-ular evolution. We illustrate the functional divergenceand evolutionary convergence in Kþ channel blockingtoxins through a series of examples.

Disclaimer: RCRdlV is funded by a FP7 COFUND PRES-SUD grant(#246556).

http://dx.doi.org/10.1016/j.toxicon.2014.08.013

6. Biosynthesis of the cyanobacterial neurotoxinsanatoxin-a and homoanatoxin-a: From the genome tothe metabolites

A. M�ejean a, b, R. Mazmouz a, b, G. Paci a, K. Moncoq b, c,L. Regad b, d, A. Combes e, V. Pichon e, O. Ploux a

a Chimie ParisTech, ENSCP, CNRS, UMR 7223, 11 rue Pierre et Marie Curie,75005 Paris, Franceb Universit�e Paris Diderot-Paris 7, 75013 Paris, Francec CNRS, UMR 7099, Institut de Biologie Physico-Chimique, 13 rue Pierre etMarie Curie, 75005 Paris, Franced INSERM, UMR-S973, MTi, 35 rue H�el�ene Brion, 75013 Paris, Francee UMR ESPCI-ParisTech-UPMC-CNRS 7195 PECSA, ESPCI ParisTech, 10 rueVauquelin, 75005 Paris, France

Anatoxin-a and its higher homolog homoanatoxin-aare two deadly neurotoxins produced by cyanobacteria.These alkaloids are potent agonists of the nicotinicacetylcholine receptor and they provoke the rapid deathof animals on ingestion (LD50 i.p. ¼ 0.2 mg/kg in mice).There are indeed frequent reports of dog poisoningsaround the world attributed to the ingestion of watercontaminated by anatoxin-a producing cyanobacteria.Because the presence of anatoxin-a producing cyano-bacteria in the environment represents a risk for humanand animal health, we have decided to study thebiosynthesis of these metabolites at the genomic, enzy-matic and analytical level. We have sequenced thegenome of the cyanobacterium Oscillatoria sp. PCC 6506,a homoanatoxin-a producer, and identified the cluster ofgenes responsible for the biosynthesis of anatoxin-a and