Toxin produced by cyanobacteria
Cyanotoxins are toxins produced by cyanobacteria (also known as blue-green algae). Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exponentially to form blooms. Blooming cyanobacteria can produce cyanotoxins in such concentrations that they can poison and even kill animals and humans. Cyanotoxins can also accumulate in other animals such as fish and shellfish, and cause poisonings such as shellfish poisoning.
Some of the most powerful natural poisons known are cyanotoxins. They include potent neurotoxins, hepatotoxins, cytotoxins, and endotoxins. The "cyano" in the term cyanobacteria refers to its colour, not to its relation to cyanides, though cyanobacteria can catabolize hydrogen cyanide during nitrogen fixation.
Exposure to cyanobacteria can result in gastro-intestinal and hayfever symptoms or pruritic skin rashes. Exposure to the cyanobacteria neurotoxin BMAA may be an environmental cause of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease, and Alzheimer's disease. There is also an interest in the military potential of biological neurotoxins such as cyanotoxins, which "have gained increasing significance as potential candidates for weaponization."
The first published report that blue-green algae or cyanobacteria could have lethal effects appeared in "Nature" in 1878. George Francis described the algal bloom he observed in the estuary of the Murray River in Australia, as "a thick scum like green oil paint, some two to six inches thick." Wildlife which drank the water died rapidly and terribly. Most reported incidents of poisoning by microalgal toxins have occurred in freshwater environments, and they are becoming more common and widespread. For example, thousands of ducks and geese died drinking contaminated water in the midwestern United States. In 2010, for the first time, marine mammals were reported to have died from ingesting cyanotoxins.
Background.
Cyanobacteria are ecologically one of the most prolific groups of phototrophic prokaryotes in both marine and freshwater habitats. Both the beneficial and detrimental aspects of cyanobacteria are of considerable significance. They are important primary producers as well as an immense source of several secondary products, including an array of toxic compounds known as cyanotoxins. Abundant growth of cyanobacteria in freshwater, estuarine, and coastal ecosystems due to increased anthropogenic eutrophication and global climate change has created serious concern toward harmful bloom formation and surface water contamination.
Cyanobacteria are considered the most primitive groups of photosynthetic prokaryotes  and possibly appeared on the Earth about 3.5 billion years ago. They are ubiquitous in nature and thrive in a variety of ecological niches ranging from desert to hot springs and ice-cold water. Cyanobacteria are an immense source of several secondary natural products with applications in the food, pharmaceuticals, cosmetics, agriculture, and energy sectors. Moreover, some species of cyanobacteria grow vigorously and form a dominant microflora in terms of their biomass and productivity in specific ecosystems. Bloom formations due to excessive growth of certain cyanobacteria followed by the production of toxic compounds have been reported in many eutrophic to hypertrophic lakes, ponds, and rivers throughout the world.
A range of toxic secondary compounds, called cyanotoxins, have been reported from cyanobacteria inhabiting freshwater and marine ecosystems. These toxic compounds are highly detrimental for survival of several aquatic organisms, wild and/or domestic animals, and humans. Aquatic organisms, including plants and animals, as well as phytoplankton and zooplankton inhabiting under toxic bloom rich ecosystems, are directly exposed to the harmful effects of different cyanotoxins. The intoxication occurring in wild and/or domestic animals and humans is either due to direct ingestion of cells of toxin producing cyanobacteria or the consumption of drinking water contaminated with cyanotoxins. The toxicity of different cyanotoxins is directly proportional to the growth of cyanobacteria and the extent of their toxin production. It has been shown that the growth of different cyanobacteria and their toxin biosynthesis is greatly influenced by different abiotic factors such as light intensity, temperature, short wavelength radiations, pH, and nutrients. Global warming and temperature gradients can significantly change species composition and favor blooms of toxic phytoplanktons.
It has been assumed that cyanotoxins play an important role in chemical defense mechanisms giving survival advantages to the cyanobacteria over other microbes or deterring predation by higher trophic levels. Cyanotoxins may also take part in chemical signalling.
Cyanotoxins are produced by cyanobacteria, a phylum of bacteria that obtain their energy through photosynthesis. The prefix "cyan" comes from the Greek meaning "a dark blue substance", and usually indicates any of a number of colours in the blue/green range of the spectrum. Cyanobacteria are commonly referred to as "blue-green algae". Traditionally they were thought of as a form of algae, and were introduced as such in older textbooks. However modern sources tend to regard this as outdated; they are now considered to be more closely related to bacteria, and the term for true "algae" is restricted to eukaryotic organisms. Like true algae, cyanobacteria are photosynthetic and contain photosynthetic pigments, which is why they are usually green or blue.
Cyanobacteria are found almost everywhere; in oceans, lakes and rivers as well as on land. They flourish in Arctic and Antarctic lakes, hotsprings and wastewater treatment plants. They even inhabit the fur of polar bears, to which they impart a greenish tinge. Cyanobacteria produce potent toxins, but they also produce helpful bioactive compounds, including substances with antitumour, antiviral, anticancer, antibiotic and antifungal activity, UV protectants and specific inhibitors of enzymes.
Harmful algal blooms.
Cyanotoxins are often implicated in what are commonly called "red tides" or "harmful algal blooms". Lakes and oceans contain many single-celled organisms called phytoplankton. Under certain conditions, particularly when nutrient concentrations are high, these organisms reproduce exponentially. The resulting dense swarm of phytoplankton is called an algal bloom; these can cover hundreds of square kilometres and can be easily seen in satellite images. Individual phytoplankton rarely live more than a few days, but blooms can last weeks.
While some of these blooms are harmless, others fall into the category of harmful algal blooms, or HABs. HABs can contain toxins or pathogens which result in fish kill and can also be fatal to humans. In marine environments, HABs are mostly caused by dinoflagellates, though species of other algae taxa can also cause HABs (diatoms, flagellates, haptophytes and raphidophytes). Marine dinoflagellate species are often toxic, but freshwater species are not known to be toxic. Neither are diatoms known to be toxic, at least to humans.
In freshwater ecosystems, algal blooms are most commonly caused by high levels of nutrients (eutrophication). The blooms can look like foam, scum or mats or like paint floating on the surface of the water, but they are not always visible. Nor are the blooms always green; they can be blue, and some cyanobacteria species are coloured brownish-red. The water can smell bad when the cyanobacteria in the bloom die.
Strong cyanobacterial blooms reduce visibility to one or two centimetres. Species which are not reliant on sight (such as cyanobacteria themselves) survive, but species which need to see to find food and partners are compromised. During the day blooming cyanobacteria saturate the water with oxygen. At night respiring aquatic organisms can deplete the oxygen to the point where sensitive species, such as certain fish, die. This is more likely to happen near the sea floor or a thermocline. Water acidity also cycles daily during a bloom, with the pH reaching 9 or more during the day and dropping to low values at night, further stressing the ecosystem. In addition, many cyanobacteria species produce potent cyanotoxins which concentrate during a bloom to the point where they become lethal to nearby aquatic organisms and any other animals in direct contact with the bloom, including birds, livestock, domestic animals and sometimes humans.
In 1991 a harmful cyanobacterial bloom affected 1,000 km of the Darling-Barwon River in Australia at an economic cost of $10M AUD.
Chemical structure.
Cyanotoxins usually target the nervous system (neurotoxins), the liver (hepatotoxins) or the skin (dermatoxins). The chemical structure of cyanotoxins falls into three broad groups: cyclic peptides, alkaloids 
and lipopolysaccharides (endotoxins).
 
Most cyanotoxins have a number of variants (analogues). As of 1999, altogether over 84 cyanotoxins were known and only a small number have been well studied.
Cyclic peptides.
A peptide is a short polymer of amino acids linked by peptide bonds. They have the same chemical structure as proteins, except they are shorter. In a cyclic peptide, the ends link to form a stable circular chain. In mammals this stability makes them resistant to the process of digestion and they can bioaccumulate in the liver. Of all the cyanotoxins, the cyclic peptides are of most concern to human health. The microcystins and nodularins poison the liver, and exposure to high doses can cause death. Exposure to low doses in drinking water over a long period of time may promote liver and other tumours.
Microcystins.
As with other cyanotoxins, microcystins were named after the first organism discovered to produce them, "Microcystis aeruginosa". However it was later found other cyanobacterial genera also produced them. There are about 60 known variants of microcystin, and several of these can be produced during a bloom. The most reported variant is microcystin-LR, possibly because the earliest commercially available chemical standard analysis was for microcystin-"LR".
Blooms containing microcystin are a problem worldwide in freshwater ecosystems. Microcystins are cyclic peptides and can be very toxic for plants and animals including humans. They bioaccumulate in the liver of fish, in the hepatopancreas of mussels, and in zooplankton. They are hepatotoxic and can cause serious damage to the liver in humans. In this way they are similar to the nodularins (below), and together the microcystins and nodularins account for most of the toxic cyanobacterial blooms in fresh and brackish waters. In 2010, a number of sea otters were poisoned by microcystin. Marine bivalves were the likely source of hepatotoxic shellfish poisoning. This was the first confirmed example of a marine mammal dying from ingesting a cyanotoxin.
Nodularins.
The first nodularin variant to be identified was nodularin-R, produced by the cyanobacterium "Nodularia spumigena". This cyanobacterium blooms in water bodies throughout the world. In the Baltic Sea, marine blooms of "Nodularia spumigena" are among some of the largest cyanobacterial mass events in the world. (Parts of nine industrialized countries drain into the Baltic Sea, which has little water exchange with the North Sea and Atlantic Ocean. It is consequently one of the more polluted bodies of water in the world (nutrient-rich, from the perspective of cyanobacteria).)
Globally, the most common toxins present in cyanobacterial blooms in fresh and brackish waters are the cyclic peptide toxins of the nodularin family. Like the microcystin family (above), nodularins are potent hepatotoxins and can cause serious damage to the liver. They present health risks for wild and domestic animals as well as humans, and in many areas pose major challenges for the provision of safe drinking water.
Alkaloids.
Alkaloids are a group of naturally occurring chemical compounds which mostly contain basic nitrogen atoms. They are produced by a large variety of organisms, including cyanobacteria, and are part of the group of natural products, also called secondary metabolites. Alkaloids act on diverse metabolic systems in humans and other animals, often with psychotropic or toxic effects. Almost uniformly, they are bitter tasting.
Anatoxin-"a".
Investigations into anatoxin-"a", also known as "Very Fast Death Factor", began in 1961 following the deaths of cows that drank from a lake containing an algal bloom in Saskatchewan, Canada. The toxin is produced by at least four different genera of cyanobacteria and has been reported in North America, Europe, Africa, Asia, and New Zealand.
Toxic effects from anatoxin-"a" progress very rapidly because it acts directly on the nerve cells (neurons) as a neurotoxin. The progressive symptoms of anatoxin-"a" exposure are loss of coordination, twitching, convulsions and rapid death by respiratory paralysis. The nerve tissues which communicate with muscles contain a receptor called the nicotinic acetylcholine receptor. Stimulation of these receptors causes a muscular contraction. The anatoxin-"a" molecule is shaped so it fits this receptor, and in this way it mimics the natural neurotransmitter normally used by the receptor, acetylcholine. Once it has triggered a contraction, anatoxin-"a" does not allow the neurons to return to their resting state, because it is not degraded by cholinesterase which normally performs this function. As a result, the muscle cells contract permanently, the communication between the brain and the muscles is disrupted and breathing stops.
The toxin was called the Very Fast Death Factor because it induced tremors, paralysis and death within a few minutes when injected into the body cavity of mice. In