Laabir, M. | Search bioRxiv

bioRxiv2026

RyR2-Dependent Calcium Leak Drives the Acute Cardiovascular Manifestations of Ciguatera Poisoning: implications for an emerging climate-sensitive cardiotoxic disease

Background: Ciguatera is the most prevalent non-bacterial seafood poisoning worldwide. It results from the consumption of fish contaminated with ciguatoxins (CTXs). Cardiovascular manifestations are frequently reported in affected patients; however, the molecular mechanisms underlying CTX-induced cardiac dysfunction remain poorly understood. Methods: We investigated the effects of purified CTX-1B and CTX-3C on human induced pluripotent stem-cell-derived ventricular cardiomyocytes. Electrophysiology, intracellular calcium cycling and contractility, and cellular structure were assessed. The RyR2 channel activity was studied in planar lipid bilayers, and molecular docking was used to identify a potential CTX-1B interaction site. Consequences on cardiac function were assessed in rats using echocardiography and EKG. Findings: We found that ciguatoxin exposure rapidly increased diastolic intracellular calcium, with severe impacts on the cardiac excitation-contraction coupling, and caused sarcomeric disorganization in human cardiomyocytes. Single-channel recordings indicated that CTX-1B prolonged RyR2 openings at resting cytosolic calcium and altered ATP-dependent gating. These findings are consistent with a state-dependent remodeling of RyR2 gating rather than uniform potentiation. Docking placed CTX-1B within the RyR2 transmembrane region, near ATP-associated regulatory elements. In rats, CTX-1B caused premature atrial contractions, ventricular ectopy, and acute cardiac dysfunction, with impaired relaxation. Interpretation: These findings identify RyR2-dependent calcium leak as a plausible contributor to ciguatoxin cardiotoxicity and extend the established model based on sodium-channel activation and altered sarcolemmal ion handling. Combined disruption of membrane excitability and intracellular calcium release could explain the rapid electrical and mechanical abnormalities associated with ciguatera. As intensive international shipping traffic and the global dispersal of harmful microalgae via ballast water expand exposure risk alongside the international seafood trade, ciguatera should be considered an emerging global cardiovascular hazard.

physiology↗

bioRxiv2025

Starvation of the bacteria Vibrio atlanticus promotes lightning group-attacks on the dinoflagellate Alexandrium pacificum

Phytoplankton serve as a source of nutrients for bacteria in the marine environment. The interactions between algae and bacteria are known to include mutualism, commensalism, competition or antagonism. This occurs in the microenvironment surrounding phytoplankton cells, the phycosphere, an interface rich in nutrients and organic molecules exuded by the cell. Here, based on in situ observations and on an in vitro interaction study, we report on a novel form of starvation-induced hunting that the cells of selected Vibrio species exert on dinoflagellates. The results showed that Vibrio atlanticus was capable of attacking and killing the dinoflagellate Alexandrium pacificum ACT03. Briefly, the observed mechanism of algal-killing consists of first, the immobilization stage involving the secretion of algicidal metabolites that disrupt the flagella of the algae. In the attack stage, Vibrios simultaneously surround algal cells at high density for a brief period without invading them. Finally, the killing stage in which the lysis and consumption of the dinoflagellates occur. By using a combination of biochemical, proteomic, molecular and fluorescence microscopy approaches, we showed that this relationship is not related to the decomposition of algal organic matter, Vibrio quorum sensing pathways, toxicity of the algae or pathogenicity of the bacterium but is conditioned by nutrient stress, iron availability and linked to the iron-vibrioferrin transport system of Vibrio atlanticus. This is the first evidence of a new mechanism that could be involved in regulating Alexandrium spp. blooms and giving Vibrio a competitive advantage in obtaining nutrients from the environment. The interaction model we propose here suggests that Vibrio could play a role in regulating the proliferation of Alexandrium spp., giving it a competitive advantage in obtaining nutrients from the environment.

microbiology↗