Source, ecological function, toxicity and resistance of Tetrodotoxin (TTX) in TTX-bearing organisms: a comprehensive review

Abstract Tetrodotoxin (TTX) can be dangerous to food security or even cause death. But TTX also has beneficial values, for example in clinical applications and drug discovery, it is used to treat arthritis, asthma and as a pain relievers. A clear understanding of the source, ecological function, toxicity, and resistance mechanisms of TTX in animals is beneficial for ecological protection, the prediction of adaptive evolution, and TTX production. Nevertheless, the origin of TTX and how organisms bearing TTX are able to resist its toxicity are still unclear. There are two hypotheses regarding the source of TTX in TTX-containing organisms: exogenous and endogenous sources. Bacteria are involved in both hypotheses. In addition, the presence of TTX-binding proteins and mutations in the gene encoding for voltage-gated sodium channels (Nav) may be responsible for TTX resistance, which remains to be elucidated. Here, we review the ecological interactions between TTX and TTX-bearing organisms. This review provides important information for ecological research on TTX, along with suggestions for scientific prevention of seafood poisoning and the development of TTX detoxification drugs.