TMT-LC-MS/MS Proteomics Reveals Brevetoxin Exposure Biomarkers in Red Tide-Affected Sea Turtles

Sea turtles are just one of the many animals harmed by Florida's red tide. Almost every year, massive algae blooms along Florida's west coast release dangerous nerve poisons into the environment. Meat-eating sea turtles, like loggerheads and Kemp's ridleys, can breathe in these poisons from the ocean spray or swallow them by eating infected prey, which can make them incredibly sick. When sick turtles wash ashore during a red tide, rescuers take them to animal hospitals to treat their symptoms, hoping they recover enough to be released back into the ocean. However, it's actually very difficult for veterinarians to take a test and prove a turtle is suffering from red tide poisoning; usually, they just assume it's the cause based on the turtle washing up during a known bloom. To make things even trickier, turtles can sometimes get sick long after the red tide has passed because it takes time for the poison to travel up the food chain.

To identify exposure biomarkers and to better understand the mechanism of toxicity of brevetoxins, researchers from Florida Gulf Coast University (Fort Myers, Florida) and Mote Marine Laboratory (Sarasota, Florida) analyzed plasma samples from red-tide exposed and healthy loggerhead and Kemp's ridley sea turtles via bottom-up tandem mass tagged (TMT)-labeled quantitative liquid chromatography tandem mass spectrometry-based proteomics. A paper based on their work was published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology.¹

What Is “Red Tide”?

Toxic algae frequently grows out of control in the ocean off the southwest coast of Florida, an event commonly known as "Florida red tide." These algae blooms happen almost every year, causing massive fish die-offs, washing sick ocean animals onto the beach, and even making people sick.^2,3 The red tide produces a suite of toxic polycyclic polyether ladder compounds known as brevetoxins (PbTxs) which act primarily on voltage-gated sodium channels (VGSCs) prevalent in excitable cell membranes, particularly in the nervous system.^4-7

What Did The Researchers Discover?

The research indicated that multiple sea turtle plasma protein abundances were significantly altered in red tide exposed turtles, including several immune system proteins like serum amyloid A5 (SAA-5; loggerheads) and CD160 antigen (Kemp's ridley). Pro-inflammatory markers serum amyloid A (SAA) and myeloid-related protein 126 (MRP-126) were measured independently in plasma of loggerhead turtles, with significant increases in these markers with red tide toxin exposure. The two species also differed in their proteomic response to red tide, indicating distinct biomarker candidates.¹

“Amid intensifying red tide events and the endangered status of these species,” write the authors of the paper,¹ “our findings provide a foundation for biomarker-based diagnosis of brevetoxicosis in sea turtles.”

References

1. Ceballos, C.; Rein, K. S.; Walsh, C. J. Brevetoxicosis in Loggerhead (Caretta caretta) and Kemp's Rdley (Lepidochelys kempii) Sea Turtles: Plasma Proteomics for Florida Red Tide Biomarkers. Comp Biochem Physiol C Toxicol Pharmacol. 2026, 110541. DOI: 10.1016/j.cbpc.2026.110541
2. Flewelling, L. J.; Naar, J. P.; Abbott, J. P. et al. Brevetoxicosis: Red Tides and Marine Mammal Mortalities. Nature 2005, 435 (7043), 755-756. DOI: 10.1038/nature435755a
3. Pierce, R. H.; Henry, M. S. Harmful Algal Toxins of the Florida Red Tide (Karenia brevis): Natural Chemical Stressors in South Florida Coastal Ecosystems. Ecotoxicology 2008, 17 (7), 623-631. DOI: 10.1007/s10646-008-0241-x
4. Hort, V.; Abadie, E.; Arnich, N, et al. Chemodiversity of Brevetoxins and Other Potentially Toxic Metabolites Produced by Karenia spp. and Their Metabolic Products in Marine Organisms. Mar Drugs 2021, 19 (12), 656. DOI: 10.3390/md19120656
5. Mackieh, R.; Abou-Nader, R.; Wehbe, R. et al. Voltage-Gated Sodium Channels: A Prominent Target of Marine Toxins. Mar Drugs 2021, 19 (10), 562. DOI: 10.3390/md19100562
6. Cocilova, C. C.; Flewelling, L. J.; Granholm, A. A. et al. Intravenous Lipid Eemulsion Treatment Reduces Symptoms of Brevetoxicosis in Turtles (Trachemys scripta). J. Zoo Wildl. Med. 2019, 50 (1), 33-44. DOI: 10.1638/2018-0032
7. Pierre, O.; Misery, L.; Talagas, M. et al. Immune Effects of the Neurotoxins Ciguatoxins and Brevetoxins. Toxicon 2018, 149, 6-19. DOI: 10.1016/j.toxicon.2018.01.002