PIRE: Advancing global strategies and understanding on the origin of ciguatera fish poisoning in tropical oceans: The Norwegian contribution

Informations

Funding country

Norway

Acronym

-

URL

-

Start date

1/1/2018

End date

12/31/2023

Budget

637,140 EUR

Fundings

Abstract

Ciguatera is the name of a disease in humans associated with the consumption of tropical fish that has accumulated a specific type of toxin from microscopic algae, called ciguatoxins (CTX). The microscopic algae belong to the genus Gambierdiscus or Fukuyoa and live on other macroscopic algae, seagrass and corals in reefs. Fish that consume the algae change the chemical structure of the toxins, which possibly increases their toxicity. Ciguatera poisoning has become a global problem due to international trade, as well as the spread of the poison-producing algae to more temperate waters. The RCN-funded project is linked to a larger NSF-funded project, CiguaPIRE. CiguaPIRE is led by the University of Southern Alabama, which is also our most important partner in the project in addition to the National Research Council of Canada and the University of Oslo. The first part of our contribution to CiguaPIRE was to map and tentatively identify different variants of Caribbean CTX (C-CTX) in toxic fish from the Gulf of Mexico. For this we used modern analytical methods that include high-resolution mass spectrometry. The work resulted in the clarification of the chemical structure of two new variants of C-CTX that are present in toxic fish samples in addition to the already known major toxins (C-CTX-1 and -2). Furthermore, we demonstrated the presence of additional toxin variants in the samples. However, these other variants were likely present in substantially lower concentrations. CTX are most often detected with a cell-based bioassay, which is a sensitive but not very selective method. To detect the toxins in a more selective way, one must use chemical methods, such as mass spectrometry. Unfortunately, CTX is a molecule that is not easy to analyze with this technique, and we have therefore developed a method that makes it easier to detect C-CTX-1 and -2 by mass spectrometry. This method is simple and straightforward, and may result in about 40-times lower detection limits. Towards the end of 2019, our partners at the University of Southern Alabama, collected fish from the Gulf of Mexico that were used to prepare enzyme fractions from their livers (so-called microsomes) for the purpose of studying how C-CTX is bio-transformed in fish. This work has resulted in new knowledge that is essential for CTX toxicology. We have demonstrated that both fish from the Gulf of Mexico, as well as Atlantic salmon, have the ability to detoxify CTX by conjugating them with glucuronic acid. We could not observe such a biotransformation reaction when the toxins were incubated with liver or human preparations. It may therefore seem that the ability to detoxify the toxins is a general trait in fish, while the ability to detoxify CTX via the same mechanism is lacking in mammals. In that case, the findings could partially explain the (high) potency of the toxins. A major collaborative breakthrough of the team was the recent identification of the algal precursor for C-CTX-1 and -2. The evidence for the compound in the algae being a precursor molecule for the toxin in the fish was obtained by isolating small quantities from an algal culture and incubation with fish microsomes. During the incubation, C-CTX-1/-2 was produced by enzymatic reaction in the microsomes.