Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus

Type Article
Date 2017-07
Language English
Author(s) Pisapia Francesco1, Sibat ManoellaORCID1, Herrenknecht Christine2, Lhaute Korian1, Gaiani Greta3, Ferron Pierre-Jean4, Fessard Valerie4, Fraga Santiago5, Nascimento Silvia M.6, Litaker R. Wayne7, Holland William C.7, Roullier Catherine2, Hess PhilippORCID1
Affiliation(s) 1 : IFREMER, Phycotoxins Lab, Rue Ile Yeu,BP 21105, F-44311 Nantes, France.
2 : Univ Nantes, LUNAM, Pharm Fac, Mer Mol Sante MMS Lab,EA2160, 9 Rue Bias, F-44035 Nantes, France.
3 : Univ Trieste, Dept Life Sci, Via Giorgieri 5, I-34127 Trieste, Italy.
4 : French Agcy Food Environm & Occupat Hlth & Safety, Toxicol Contaminants Unit, ANSES Lab, 10 B Rue Claude Bourgelat, F-35133 Javene, France.
5 : Ctr Oceanog Vigo, IEO, Subida Radio Faro 50, Vigo 36390, Spain.
6 : Univ Fed Estado Rio De Janeiro UNIRIO, Dept Ecol & Recursos Marinhos, Lab Microalgas Marinhas, BR-22290240 Rio De Janeiro, Brazil.
7 : NOAA, Natl Ocean Serv, Natl Ctr Coastal Ocean Sci, CCFHR, 101 Pivers Isl Rd, Beaufort, NC 28516 USA.
Source Marine Drugs (1660-3397) (Mdpi Ag), 2017-07 , Vol. 15 , N. 7 , P. 220 (1-31)
DOI 10.3390/md15070220
WOS© Times Cited 21
Keyword(s) Gambierdiscus excentricus, maitotoxin-4, bioguided fractionation, size-exclusion chromatography (LH-20), neuro-2a (N2a) assay, LC-HRMS/MS (Q-Tof 6550), LC-LRMS/MS (API4000 QTrap)
Abstract

Maitotoxins (MTXs) are among the most potent toxins known. These toxins are produced by epi-benthic dinoflagellates of the genera Gambierdiscus and Fukuyoa and may play a role in causing the symptoms associated with Ciguatera Fish Poisoning. A recent survey revealed that, of the species tested, the newly described species from the Canary Islands, G. excentricus, is one of the most maitotoxic. The goal of the present study was to characterize MTX-related compounds produced by this species. Initially, lysates of cells from two Canary Island G. excentricus strains VGO791 and VGO792 were partially purified by (i) liquid-liquid partitioning between dichloromethane and aqueous methanol followed by (ii) size-exclusion chromatography. Fractions from chromatographic separation were screened for MTX toxicity using both the neuroblastoma neuro-2a (N2a) cytotoxicity and Ca2+ flux functional assays. Fractions containing MTX activity were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to pinpoint potential MTX analogs. Subsequent non-targeted HRMS analysis permitted the identification of a novel MTX analog, maitotoxin-4 (MTX4, accurate mono-isotopic mass of 3292.4860 Da, as free acid form) in the most toxic fractions. HRMS/MS spectra of MTX4 as well as of MTX are presented. In addition, crude methanolic extracts of five other strains of G. excentricus and 37 other strains representing one Fukuyoa species and ten species, one ribotype and one undetermined strain/species of Gambierdiscus were screened for the presence of MTXs using low resolution tandem mass spectrometry (LRMS/MS). This targeted analysis indicated the original maitotoxin (MTX) was only present in one strain (G. australes S080911_1). Putative maitotoxin-2 (p-MTX2) and maitotoxin-3 (p-MTX3) were identified in several other species, but confirmation was not possible because of the lack of reference material. Maitotoxin-4 was detected in all seven strains of G. excentricus examined, independently of their origin (Brazil, Canary Islands and Caribbean), and not detected in any other species. MTX4 may therefore serve as a biomarker for the highly toxic G. excentricus in the Atlantic area.

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Pisapia Francesco, Sibat Manoella, Herrenknecht Christine, Lhaute Korian, Gaiani Greta, Ferron Pierre-Jean, Fessard Valerie, Fraga Santiago, Nascimento Silvia M., Litaker R. Wayne, Holland William C., Roullier Catherine, Hess Philipp (2017). Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus. Marine Drugs, 15(7), 220 (1-31). Publisher's official version : https://doi.org/10.3390/md15070220 , Open Access version : https://archimer.ifremer.fr/doc/00392/50320/