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The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus—Just a False Positive?

Swedish Species Information Centre, Swedish University of Agricultural Sciences, 75007 Uppsala, Sweden
Division of Biotechnology, Lund University, 22100 Lund, Sweden
Department of Biological and Environmental Sciences, University of Gothenburg, 40530 Gothenburg, Sweden
Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L32AJ, UK
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, 75237 Uppsala, Sweden
Linnaeus University Centre for Biomaterials Chemistry, Department of Chemistry and Biomedical Sciences, Linnaeus University, 39234 Kalmar, Sweden
Authors to whom correspondence should be addressed.
Academic Editor: Marcel Jaspars
Mar. Drugs 2016, 14(4), 63;
Received: 19 November 2015 / Revised: 14 March 2016 / Accepted: 15 March 2016 / Published: 25 March 2016
PDF [1636 KB, uploaded 25 March 2016]


We test previous claims that the bacteria Vibrio alginolyticus produces tetrodotoxin (TTX) when living in symbiosis with the nemertean Lineus longissimus by a setup with bacteria cultivation for TTX production. Toxicity experiments on the shore crab, Carcinus maenas, demonstrated the presence of a paralytic toxin, but evidence from LC-MS and electrophysiological measurements of voltage-gated sodium channel–dependent nerve conductance in male Wistar rat tissue showed conclusively that this effect did not originate from TTX. However, a compound of similar molecular weight was found, albeit apparently non-toxic, and with different LC retention time and MS/MS fragmentation pattern than those of TTX. We conclude that C. maenas paralysis and death likely emanate from a compound <5 kDa, and via a different mechanism of action than that of TTX. The similarity in mass between TTX and the Vibrio-produced low-molecular-weight, non-toxic compound invokes that thorough analysis is required when assessing TTX production. Based on our findings, we suggest that re-examination of some published claims of TTX production may be warranted. View Full-Text
Keywords: LC-MS; mucus; axonal conductance; Vibrio; nemertean; tetrodotoxin LC-MS; mucus; axonal conductance; Vibrio; nemertean; tetrodotoxin

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Strand, M.; Hedström, M.; Seth, H.; McEvoy, E.G.; Jacobsson, E.; Göransson, U.; Andersson, H.S.; Sundberg, P. The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus—Just a False Positive? Mar. Drugs 2016, 14, 63.

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