One of the dominant dinoflagellates originally identified in the 2025 bloom in South Australia is Karenia mikimotoi. It causes mortality across a wide range of species due to a cytotoxic action that leads to the destruction of susceptible cells and tissues with which it comes into contact1. The maximum cytotoxic effect requires the dinoflagellate cells to be intact: once the cells break down, due to turbulent sea conditions, for example, the cytotoxic action is reduced2. Nevertheless, sea foams containing high levels of Karenia mikimotoi may retain some of its cytotoxic properties.
The precise chemical nature of the toxin in Karenia mikimotoi is not known. However, its mode of action probably reflects the biochemical nature and modes of action of cytotoxins in other related dinoflagellate species that have been characterised, such as karmitoxin and karlotoxin from Karlodinium spp or brevisucenals from Karenia brevisulcata (see details below).
In November 2025, Karenia cristata was identified as a dominant species in the current bloom. It produces significant levels of brevetoxins, which are primarily neurotoxins. However studies on Karenia brevis, another major producer of brevetoxin, not found in South Australia, have shown that it also possesses a potent cytotoxin that it used against other microalgae in the bloom3. Similarly, Karenia brevisulcata, produces highly potent cytotoxins (brevisucenals) in addition to brevetoxin-like neurotoxins (brevesulcatic acids)4. It is therefore very likely that Karenia cristata also possesses a comparable cytotoxin5. Indeed, another group of dinoflagellates, Alexandrium spp, known to produce potent neurotoxins including saxitoxin (see more about saxitoxin below), also produce so-called bioactive extracellular compounds, that have marked cytolytic or cytotoxic effects, but whose chemical identities remain unknown6.
Given the mix of species in the bloom and observations that some species produce more than one type of toxin, it is probably that some of the cytotoxic effects are due to interactions between multiple agents.7
The cytotoxic action in this case is due to the damage of the membrane that surrounds all cells, leading to cytolysis, the breakdown of the cell itself. How this happens is complicated! The following explanation is greatly simplified.
Let’s start with some basic information about the structure of cells and how they differ from their surrounding external and internal environments.
The internal environment of a cell is vastly different from that outside the cell. The bulk of the internal environment is comprised of the cytoplasm (yellow), a complex mix of salts, signalling molecules, energy sources and proteins in addition to a collection of intracellular structures (intracellular organelles), each with a discrete function. These internal structures include the nucleus (containing genetic information, central dark blue oval in the illustration), mitochondria (producing energy for metabolism, the grey football shapes), ribosomes (making proteins), lysosomes (getting rid of metabolic waste) and cytoskeleton (holding everything together).
The difference is most stark if we look at the concentrations of salt, sodium chloride (NaCl), inside and outside the cell. There is very little sodium salt in the cytoplasm (instead it is mostly potassium salt). In a vertebrate such as a fish (or human!), the concentration of salt in the body fluids, most notably blood plasma, is more than 10 times higher than that inside the cells. Even more dramatic, the concentration of salt in sea water is more than 4 times higher again. The numbers in the diagram above are typical concentrations of NaCl in each type of fluid. The units are mM = millimolar, a measure of concentration.
The salt levels inside the cell have to be maintained within narrow limits for the cell to function properly. This special internal environment of the cell is separated from the external environment by the cell membrane, indicated by the grey outline in the diagram. The membrane is incredibly thin: 10nm, where 1nm (nanometre) = 1 millionth of a millimetre. Structurally, it consists of a lipid bilayer, ie, two layers of lipid molecules (fat-like molecules), within which are embedded various proteins and sugars that all have important cellular functions, such as ion channels (for electrical activity); receptors (for neuronal or endocrine signalling); and cell-adhesion molecules (for holding tissues together).
How Karenia mikimotoi causes cytotoxicity
When cytotoxic Karenia mikimotoi organisms (dark green arrowheads in the diagram) contact other cell membranes, they disrupt their molecular structure causing the membrane to develop pores or even completely fall apart. Once this happens, the membrane can no longer maintain separation between the internal and external environments of the cell: amongst other things, sodium will flow into the cell, water will flow out, and the whole structural integrity will be lost.
Most metabolic functions of the cell require the composition of the internal environment to be highly regulated and so they will also be disrupted by damage to the cell membrane. The end results is that the cell dies and falls apart: this is cytolysis. It usually happens very quickly once the cell membrane is damaged beyond the point it can repair itself.
When red blood cells are exposed to cytolytic agents, such as Karenia mikimotoi, their membranes break down in the same way as any other cell. Consequently, their haemoglobin, the red protein that transports oxygen in the blood, leaks out into the surrounding body fluids. This is haemolysis. Mammalian red blood cells are very fragile and they are often used in laboratories to test for haemolytic and cytolytic actions of toxins.
As its name suggests, the lipid bilayer of the cell membrane is only two molecules thick. There are many different lipids in the membrane, but the dominant forms are phospholipids, so-called because they have a phosphate group at one end (the ‘head’) of the molecule. Lipids, like most fats are not soluble in water. However, phosphates are water-soluble. This means that the phospholipid molecule is effectively water-soluble (hydrophilic) at one end (the phosphate head) and water-insoluble at the other end (the lipid tails). When the phospholipids come together to assemble the two-layered cell membrane, the outer layer is oriented with the phosphate heads facing the extra-cellular environment. The inner layer is a mirror-image with the phosphate heads facing the intra-cellular environment (the cytoplasm). The lipid tails of each layer are oriented towards the inside of the membrane. This lipid-rich microenvironment inside the membrane repels water (ie, it is hydrophobic) which is a key element in creating the barrier to salt and water transfer between the extra-cellular and intra-cellular environments.
At the normal body temperature of an animal, the lipid bilayer is largely fluid. One the reasons for differences in membrane lipid composition in different animals is to allow for their different body temperatures, eg 37ºC for mammals, but maybe only 15ºC for a fish. The lipid bilayer contains a large variety of other molecules, mostly proteins and some complex sugars. The proteins include receptors for neurotransmitters and hormones, ion channels, various enzymes and structural proteins. Some are mostly in the outer lipid layer, some are mostly in the inner layer, and some traverse both layers. Because of the fluid nature of the lipid bilayer, many of the embedded proteins can move around within the membrane. This property of the membrane and its proteins is called the fluid mosaic model.
Although the exact nature of the cytolytic agent in Karenia mikimotoi is not known, it is probably some kind of lipid, most likely a polyunsaturated fatty acid (PUFA), although other lipids, such as glycolipids8, may be involved as well. PUFAs are a large family of molecules, produced mainly by plants. Some are beneficial components of the diet, but others can be cytolytic. There are multiple ways in which they can disrupt cell membranes. The probable first step is to displace some of the intrinsic membrane lipids leading to disruption of the lipid bilayer. PUFAs also can interact with membrane lipids chemically leading to the production of reactive oxygen species (ROS), such as hydrogen peroxide and superoxides, which in turn can cause more damage to the membrane structure, including the membrane proteins. Almost by definition, ROS are very short lived in the environment, and exert most of the damaging effects on cells at molecular scales. Most cell types have a range of mechanisms to prevent damage from ROS, such as superoxide dismutase enzymes, but these mechanisms can be overwhelmed by high levels of extracellular PUFAs9. Nevertheless, there is good evidence that the main cytolytic effect of Karenia mikimotoi does not involve any significant contribution from ROS, even in strains that produce high levels of ROS10. Based on studies of other Karenia species, it is possible there is more than one cytotoxic agent, which have differing solubilities and toxicities11.
The cytolytic actions of another group of dinoflagellates, Karlodinium spp., are much better understood. These species produce highly lipophilic polyketides, such as karmitoxin and karlotoxin that target specific groups of fatty acids in cell membranes, including cholesterol, to form large leaky pores in the membranes.12 The consequences on gill function of fish is similar to that described for Karenia mikimotoi.
Cytotoxins from other marine organisms, such as jelly fish or sea snakes, can work in very different ways. Some are enzymes (phospholipases) that break down the phosphate heads of the membrane phospholipids. Others are specialised proteins (cytolysins) that embed themselves into the cell membrane and then self-assemble into pores that make the cells leaky.
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Unlike most marine neurotoxins, the cytotoxic effects of Karenia mikimotoi do not seem to persist in organisms that have been killed by the bloom. This is probably due to a combination of the nature of the toxic effect itself, which requires direct contact with the Karenia organisms and the high likelihood that the chemical mediator of the toxic is broken down in the gut, should intact Karenia reach there.
Anecdotal observations suggest that sea birds such as Silver Gulls have been feeding on freshly washed up dead fish, presumably killed by exposure to Karenia mikimotoi, with no obvious signs of poisoning in the birds. This is consistent with previous reports that these cytotoxic agents do not build up in animal tissues. However, if they were to eat fish or other animals killed by brevetoxin, they may well be poisoned by the toxin that has accumulated in their tissues13. Click here to see more about brevetoxin.
Selected references
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Chang FH (2011) Toxic effects of three closely-related dinoflagellates, Karenia concordia, K. brevisulcata and K. mikimotoi (Gymnodiniales, Dinophyceae) on other microalgal species. Harmful Algae 10: 181-187, http://dx.doi.org/10.1016/j.hal.2010.09.004
Li X et al (2019) A review of Karenia mikimotoi: Bloom events, physiology, toxicity and toxic mechanism. Harmful Algae 90: 101702, https://doi.org/10.1016/j.hal.2019.101702 ;
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↩︎ - Poulin RX et al (2017) Karenia brevis allelopathy compromises the lipidome, membrane integrity, and photosynthesis of competitors. Scientific Reports 8: 9572, https://doi.org/10.1038/s41598-018-27845-9 ;
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↩︎ - Li X et al (2019) A review of Karenia mikimotoi: Bloom events, physiology, toxicity and toxic mechanism. Harmful Algae 90: 101702, https://doi.org/10.1016/j.hal.2019.101702 ;
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↩︎ - Liu Z et al (2025) Growth interactions between the dinoflagellate Karenia selliformis and the diatom Chaetoceros diadema. European Journal of Phycology https://doi.org/10.1080/09670262.2025.2524341
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↩︎ - Hort V et al (2021) Chemodiversity of brevetoxins and other potentially toxic metabolites produced by Karenia spp. and their metabolic products in marine organisms. Marine Drugs 19: 656, https://doi.org/10.3390/md19120656;
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