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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (16 October 2021) | Viewed by 32357

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Prof. Dr. Jordi Molgó

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CEA, INRAE, Institut des Sciences du Vivant Frédéric Joliot, Département Médicaments et Technologies pour la Santé (DMTS), Equipe Mixte de Recherche CNRS n° 9004, Service d’Ingénierie Moléculaire pour la Santé (SIMoS), Université Paris-Saclay, Bâtiment 152, rue de la Biologie, Point courrier 24, F-91191 Gif sur Yvette, France
Interests: natural toxins from marine and terrestrial organisms; voltage-gated ion channels; ligand gated channels; nicotinic acetylcholine receptors; cholinesterases; IP3 receptors; cell signaling; synaptic transmission; neuromuscular transmission; transmitter release
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Dear Colleagues,

Marine environments are known to contain microorganisms such as bacteria, cyanobacteria, dinoflagellates, diatoms, and fungi. When environmental conditions are favorable for their massive proliferation (increase in temperature, richness in nutrients, salinity, luminosity, etc.), these unicellular microorganisms may manifest their potential toxicity by producing marine biotoxins and contaminating invertebrate and vertebrate marine organisms through the food web. Undeniably, these marine biotoxins may constitute a risk for human consumers of contaminated shellfish and fish. Also, the vectorial transfer of marine biotoxins to crabs, fish, birds, and marine mammals constitutes a menace for wildlife. Most marine biotoxins belong to different families of organic molecules, with diverse and rich chemical structures, and new marine biotoxins of organic and protein nature are being described. The vast family of marine biotoxins act on different targets including subtypes of voltage-gated sodium ion channels, potassium or calcium channels, ionotropic receptors—like glutamate receptors (AMPA, Kainate, and NMDA receptors), nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA_A receptors)—and G protein-coupled receptors. Therefore, important efforts are being made to decipher the cellular and molecular signaling pathways used by marine biotoxins to exert their toxic activity.

This special issue of Marine Drugs is open to original research articles and reviews dealing with marine biotoxins and the following subjects:

Identification of new and emergent marine biotoxins
Marine biotoxins from identified bacteria, cyanobacteria, fungi, dinoflagellates, and diatoms
Characterization of new biotoxin chemical structures
Biosynthetic pathways involved in biotoxin production
Cellular and molecular signaling pathways implicated in marine biotoxin action
Pharmacology and structure–activity relationship
Bio-distribution, metabolism, acute and chronic toxicity in animal models
Molecular modeling of marine biotoxins with their putative receptors
Potential therapeutic uses of marine biotoxins

Prof. Dr. Jordi Molgó
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Marine biotoxins
Biosynthesis
Pharmacology
Molecular target(s)
Signaling pathways
Metabolism
Toxicity
Molecular modeling
Therapeutic potential

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Related Special Issues

Marine Biotoxins 2.0 in Marine Drugs (4 articles)
Marine Biotoxins 3.0 in Marine Drugs (6 articles)

Published Papers (9 papers)

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Research

20 pages, 2959 KiB

Open AccessArticle

Sulfo-Gambierones, Two New Analogs of Gambierone Produced by Gambierdiscus excentricus

by Thomas Yon, Manoëlla Sibat, Elise Robert, Korian Lhaute, William C. Holland, R. Wayne Litaker, Samuel Bertrand, Philipp Hess and Damien Réveillon

Mar. Drugs 2021, 19(12), 657; https://doi.org/10.3390/md19120657 - 24 Nov 2021

Cited by 16 | Viewed by 2529

Abstract

Ciguatera poisoning is caused by the ingestion of fish or shellfish contaminated with ciguatoxins produced by dinoflagellate species belonging to the genera Gambierdiscus and Fukuyoa. Unlike in the Pacific region, the species producing ciguatoxins in the Atlantic Ocean have yet to be definitely identified, though some ciguatoxins responsible for ciguatera have been reported from fish. Previous studies investigating the ciguatoxin-like toxicity of Atlantic Gambierdiscus species using Neuro2a cell-based assay identified G. excentricus as a potential toxin producer. To more rigorously characterize the toxin profile produced by this species, a purified extract from 124 million cells was prepared and partial characterization by high-resolution mass spectrometry was performed. The analysis revealed two new analogs of the polyether gambierone: sulfo-gambierone and dihydro-sulfo-gambierone. Algal ciguatoxins were not identified. The very low ciguatoxin-like toxicity of the two new analogs obtained by the Neuro2a cell-based assay suggests they are not responsible for the relatively high toxicity previously observed when using fractionated G. excentricus extracts, and are unlikely the cause of ciguatera in the region. These compounds, however, can be useful as biomarkers of the presence of G. excentricus due to their sensitive detection by mass spectrometry. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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24 pages, 2775 KiB

Open AccessArticle

Deep-Water Fish Are Potential Vectors of Ciguatera Poisoning in the Gambier Islands, French Polynesia

by Hélène Taiana Darius, Taina Revel, Philippe Cruchet, Jérôme Viallon, Clémence Mahana iti Gatti, Manoëlla Sibat, Philipp Hess and Mireille Chinain

Mar. Drugs 2021, 19(11), 644; https://doi.org/10.3390/md19110644 - 17 Nov 2021

Cited by 10 | Viewed by 4033

Abstract

Ciguatera poisoning (CP) cases linked to the consumption of deep-water fish occurred in 2003 in the Gambier Islands (French Polynesia). In 2004, on the request of two local fishermen, the presence of ciguatoxins (CTXs) was examined in part of their fish catches, i.e., 22 specimens representing five deep-water fish species. Using the radioactive receptor binding assay (rRBA) and mouse bioassay (MBA), significant CTX levels were detected in seven deep-water specimens in Lutjanidae, Serranidae, and Bramidae families. Following additional purification steps on the remaining liposoluble fractions for 13 of these samples (kept at −20 °C), these latter were reanalyzed in 2018 with improved protocols of the neuroblastoma cell-based assay (CBA-N2a) and liquid chromatography tandem mass spectrometry (LC–MS/MS). Using the CBA-N2a, the highest CTX-like content found in a specimen of Eumegistus illustris (Bramidae) was 2.94 ± 0.27 µg CTX1B eq. kg⁻¹. Its toxin profile consisted of 52-epi-54-deoxyCTX1B, CTX1B, and 54-deoxyCTX1B, as assessed by LC–MS/MS. This is the first study demonstrating that deep-water fish are potential ciguatera vectors and highlighting the importance of a systematic monitoring of CTXs in all exploited fish species, especially in ciguatera hotspots, including deep-water fish, which constitute a significant portion of the commercial deep-sea fisheries in many Asian–Pacific countries. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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16 pages, 2342 KiB

Open AccessArticle

Changing Trends in Paralytic Shellfish Poisonings Reflect Increasing Sea Surface Temperatures and Practices of Indigenous and Recreational Harvesters in British Columbia, Canada

by Lorraine McIntyre, Aroha Miller and Tom Kosatsky

Mar. Drugs 2021, 19(10), 568; https://doi.org/10.3390/md19100568 - 14 Oct 2021

Cited by 11 | Viewed by 4690

Abstract

Paralytic shellfish poisoning (PSP) occurs when shellfish contaminated with saxitoxin or equivalent paralytic shellfish toxins (PSTs) are ingested. In British Columbia, Canada, documented poisonings are increasing in frequency based on 62 investigations identified from 1941–2020. Two PSP investigations were reported between 1941 and 1960 compared to 31 since 2001 (p < 0.0001) coincident with rising global temperatures (r² = 0.76, p < 0.006). The majority of PSP investigations (71%) and cases (69%) were linked to self-harvested shellfish. Far more investigations involved harvests by indigenous communities (24%) than by commercial and recreational groups. Single-case-exposure investigations increased by more than 3.5 times in the decade 2011–2020 compared to previous periods. Clams (47%); mussels (26%); oysters (14%); scallops (6%); and, in more recent years, crabs (4%) were linked to illnesses. To guide understanding of self-harvesting consumption risks, we recommend collecting data to determine when PST-producing algae are present in high concentrations, improving the quality of data in online shellfish harvest maps to include dates of last testing; biotoxin testing results; and a description of bivalve species tested. Over reliance on toxin results in biomonitored species may not address actual consumption risks for unmonitored species harvested from the same area. We further recommend introducing phytoplankton monitoring in remote indigenous communities where self-harvesting is common and toxin testing is unavailable, as well as continuing participatory education about biotoxin risks in seafoods. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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14 pages, 6266 KiB

Open AccessArticle

Guidance Level for Brevetoxins in French Shellfish

by Nathalie Arnich, Eric Abadie, Zouher Amzil, Marie-Yasmine Dechraoui Bottein, Katia Comte, Estelle Chaix, Nicolas Delcourt, Vincent Hort, César Mattei, Jordi Molgó and Raphaele Le Garrec

Mar. Drugs 2021, 19(9), 520; https://doi.org/10.3390/md19090520 - 15 Sep 2021

Cited by 14 | Viewed by 3791

Abstract

Brevetoxins (BTXs) are marine biotoxins responsible for neurotoxic shellfish poisoning (NSP) after ingestion of contaminated shellfish. NSP is characterized by neurological, gastrointestinal and/or cardiovascular symptoms. The main known producer of BTXs is the dinoflagellate Karenia brevis, but other microalgae are also suspected to synthesize BTX-like compounds. BTXs are currently not regulated in France and in Europe. In November 2018, they have been detected for the first time in France in mussels from a lagoon in the Corsica Island (Mediterranean Sea), as part of the network for monitoring the emergence of marine biotoxins in shellfish. To prevent health risks associated with the consumption of shellfish contaminated with BTXs in France, a working group was set up by the French Agency for Food, Environmental and Occupational Health & Safety (Anses). One of the aims of this working group was to propose a guidance level for the presence of BTXs in shellfish. Toxicological data were too limited to derive an acute oral reference dose (ARfD). Based on human case reports, we identified two lowest-observed-adverse-effect levels (LOAELs). A guidance level of 180 µg BTX-3 eq./kg shellfish meat is proposed, considering a protective default portion size of 400 g shellfish meat. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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19 pages, 2340 KiB

Open AccessArticle

Pacific-Ciguatoxin-2 and Brevetoxin-1 Induce the Sensitization of Sensory Receptors Mediating Pain and Pruritus in Sensory Neurons

by Ophélie Pierre, Maxime Fouchard, Nelig Le Goux, Paul Buscaglia, Raphaël Leschiera, Richard J. Lewis, Olivier Mignen, Joachim W. Fluhr, Laurent Misery and Raphaële Le Garrec

Mar. Drugs 2021, 19(7), 387; https://doi.org/10.3390/md19070387 - 6 Jul 2021

Cited by 2 | Viewed by 3260

Abstract

Ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning syndromes are induced by the consumption of seafood contaminated by ciguatoxins and brevetoxins. Both toxins cause sensory symptoms such as paresthesia, cold dysesthesia and painful disorders. An intense pruritus, which may become chronic, occurs also in CFP. No curative treatment is available and the pathophysiology is not fully elucidated. Here we conducted single-cell calcium video-imaging experiments in sensory neurons from newborn rats to study in vitro the ability of Pacific-ciguatoxin-2 (P-CTX-2) and brevetoxin-1 (PbTx-1) to sensitize receptors and ion channels, (i.e., to increase the percentage of responding cells and/or the response amplitude to their pharmacological agonists). In addition, we studied the neurotrophin release in sensory neurons co-cultured with keratinocytes after exposure to P-CTX-2. Our results show that P-CTX-2 induced the sensitization of TRPA1, TRPV4, PAR2, MrgprC, MrgprA and TTX-r NaV channels in sensory neurons. P-CTX-2 increased the release of nerve growth factor and brain-derived neurotrophic factor in the co-culture supernatant, suggesting that those neurotrophins could contribute to the sensitization of the aforementioned receptors and channels. Our results suggest the potential role of sensitization of sensory receptors/ion channels in the induction or persistence of sensory disturbances in CFP syndrome. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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17 pages, 2963 KiB

Open AccessArticle

Electrophysiological Evaluation of Pacific Oyster (Crassostrea gigas) Sensitivity to Saxitoxin and Tetrodotoxin

by Floriane Boullot, Caroline Fabioux, Hélène Hégaret, Pierre Boudry, Philippe Soudant and Evelyne Benoit

Mar. Drugs 2021, 19(7), 380; https://doi.org/10.3390/md19070380 - 30 Jun 2021

Cited by 4 | Viewed by 2895

Abstract

Pacific oysters (Crassostrea gigas) may bio-accumulate high levels of paralytic shellfish toxins (PST) during harmful algal blooms of the genus Alexandrium. These blooms regularly occur in coastal waters, affecting oyster health and marketability. The aim of our study was to analyse the PST-sensitivity of nerves of Pacific oysters in relation with toxin bio-accumulation. The results show that C. gigas nerves have micromolar range of saxitoxin (STX) sensitivity, thus providing intermediate STX sensitivity compared to other bivalve species. However, theses nerves were much less sensitive to tetrodotoxin. The STX-sensitivity of compound nerve action potential (CNAP) recorded from oysters experimentally fed with Alexandrium minutum (toxic-alga-exposed oysters), or Tisochrysis lutea, a non-toxic microalga (control oysters), revealed that oysters could be separated into STX-resistant and STX-sensitive categories, regardless of the diet. Moreover, the percentage of toxin-sensitive nerves was lower, and the STX concentration necessary to inhibit 50% of CNAP higher, in recently toxic-alga-exposed oysters than in control bivalves. However, no obvious correlation was observed between nerve sensitivity to STX and the STX content in oyster digestive glands. None of the nerves isolated from wild and farmed oysters was detected to be sensitive to tetrodotoxin. In conclusion, this study highlights the good potential of cerebrovisceral nerves of Pacific oysters for electrophysiological and pharmacological studies. In addition, this study shows, for the first time, that C. gigas nerves have micromolar range of STX sensitivity. The STX sensitivity decreases, at least temporary, upon recent oyster exposure to dinoflagellates producing PST under natural, but not experimental environment. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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24 pages, 7538 KiB

Open AccessArticle

Hemolytic Activity in Relation to the Photosynthetic System in Chattonella marina and Chattonella ovata

by Ni Wu, Mengmeng Tong, Siyu Gou, Weiji Zeng, Zhuoyun Xu and Tianjiu Jiang

Mar. Drugs 2021, 19(6), 336; https://doi.org/10.3390/md19060336 - 12 Jun 2021

Cited by 8 | Viewed by 2966

Abstract

Chattonella species, C. marina and C. ovata, are harmful raphidophycean flagellates known to have hemolytic effects on many marine organisms and resulting in massive ecological damage worldwide. However, knowledge of the toxigenic mechanism of these ichthyotoxic flagellates is still limited. Light was reported to be responsible for the hemolytic activity (HA) of Chattonella species. Therefore, the response of photoprotective, photosynthetic accessory pigments, the photosystem II (PSII) electron transport chain, as well as HA were investigated in non-axenic C. marina and C. ovata cultures under variable environmental conditions (light, iron and addition of photosynthetic inhibitors). HA and hydrogen peroxide (H₂O₂) were quantified using erythrocytes and pHPA assay. Results confirmed that% HA of Chattonella was initiated by light, but was not always elicited during cell division. Exponential growth of C. marina and C. ovata under the light over 100 µmol m⁻² s⁻¹ or iron-sufficient conditions elicited high hemolytic activity. Inhibitors of PSII reduced the HA of C. marina, but had no effect on C. ovata. The toxicological response indicated that HA in Chattonella was not associated with the photoprotective system, i.e., xanthophyll cycle and regulation of reactive oxygen species, nor the PSII electron transport chain, but most likely occurred during energy transport through the light-harvesting antenna pigments. A positive, highly significant relationship between HA and chlorophyll (chl) biosynthesis pigments, especially chl c2 and chl a, in both species, indicated that hemolytic toxin may be generated during electron/energy transfer through the chl c2 biosynthesis pathway. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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16 pages, 2626 KiB

Open AccessArticle

Tetrodotoxins (TTXs) and Vibrio alginolyticus in Mussels from Central Adriatic Sea (Italy): Are They Closely Related?

by Simone Bacchiocchi, Debora Campacci, Melania Siracusa, Alessandra Dubbini, Francesca Leoni, Tamara Tavoloni, Stefano Accoroni, Stefania Gorbi, Maria Elisa Giuliani, Arianna Stramenga and Arianna Piersanti

Mar. Drugs 2021, 19(6), 304; https://doi.org/10.3390/md19060304 - 25 May 2021

Cited by 17 | Viewed by 3905

Abstract

Tetrodotoxins (TTXs), potent neurotoxins, have become an increasing concern in Europe in recent decades, especially because of their presence in mollusks. The European Food Safety Authority published a Scientific Opinion setting a recommended threshold for TTX in mollusks of 44 µg equivalent kg⁻¹ and calling all member states to contribute to an effort to gather data in order to produce a more exhaustive risk assessment. The objective of this work was to assess TTX levels in wild and farmed mussels (Mytilus galloprovincialis) harvested in 2018–2019 along the coastal area of the Marche region in the Central Adriatic Sea (Italy). The presence of Vibrio spp. carrying the non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes, which are suspected to be involved in TTX biosynthesis, was also investigated. Out of 158 mussel samples analyzed by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry (HILIC-MS/MS), 11 (7%) contained the toxins at detectable levels (8–26 µg kg⁻¹) and 3 (2%) contained levels above the EFSA safety threshold (61–76 µg kg⁻¹). Contaminated mussels were all harvested from natural beds in spring or summer. Of the 2019 samples, 70% of them contained V. alginolyticus strains with the NRPS and/or PKS genes. None of the strains containing NRPS and/or PKS genes showed detectable levels of TTXs. TTXs in mussels are not yet a threat in the Marche region nor in Europe, but further investigations are surely needed. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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20 pages, 2703 KiB

Open AccessArticle

Lipophilic Toxins in Wild Bivalves from the Southern Gulf of California, Mexico

by Ignacio Leyva-Valencia, Jesús Ernestina Hernández-Castro, Christine J. Band-Schmidt, Andrew D. Turner, Alison O’Neill, Erick J. Núñez-Vázquez, David J. López-Cortés, José J. Bustillos-Guzmán and Francisco E. Hernández-Sandoval

Mar. Drugs 2021, 19(2), 99; https://doi.org/10.3390/md19020099 - 9 Feb 2021

Cited by 9 | Viewed by 2991

Abstract

Most of the shellfish fisheries of Mexico occur in the Gulf of California. In this region, known for its high primary productivity, blooms of diatoms and dinoflagellates are common, occurring mainly during upwelling events. Dinoflagellates that produce lipophilic toxins are present, where some outbreaks related to okadaic acid and dinophisystoxins have been recorded. From January 2015 to November 2017 samples of three species of wild bivalve mollusks were collected monthly in five sites in the southern region of Bahía de La Paz. Pooled tissue extracts were analyzed using LC-MS/MS to detect lipophilic toxins. Eighteen analogs of seven toxin groups, including cyclic imines were identified, fortunately individual toxins did not exceed regulatory levels and also the total toxin concentration for each bivalve species was lower than the maximum permitted level for human consumption. Interspecific differences in toxin number and concentration were observed in three species of bivalves even when the samples were collected at the same site. Okadaic acid was detected in low concentrations, while yessotoxins and gymnodimines had the highest concentrations in bivalve tissues. Although in low quantities, the presence of cyclic imines and other lipophilic toxins in bivalves from the southern Gulf of California was constant. Full article

(This article belongs to the Special Issue Marine Biotoxins)

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