Ergot (), or ergot fungi, is a group of fungi of the genus Claviceps.

The most prominent member of this group is Claviceps purpurea (rye ergot fungus). This fungus grows on rye and related plants, and produces alkaloids that can cause ergotism in humans and other mammals who consume grains contaminated with its fruiting structure (called ergot sclerotium).

Claviceps includes about 50 known species, mostly in the tropical regions. Economically significant species include C. purpurea (parasitic on grasses and cereals), C. fusiformis (on pearl millet, buffel grass), C. paspali (on dallis grass), C. africana (on sorghum) and C. lutea (on paspalum). C. purpurea most commonly affects outcrossing species such as rye (its most common host), as well as triticale, wheat and barley. It affects oats only rarely.

C. purpurea has at least three races, or varieties, which differ in their host specificity:

  • G1 – land grasses of open meadows and fields;
  • G2 – grasses from moist, forest and mountain habitats;
  • G3 (C. purpurea var. spartinae) – salt marsh grasses (Spartina, Distichlis).

Life cycle

An ergot kernel, called a sclerotium, develops when a spore of fungal species of the genus Claviceps infects a floret of flowering grass or cereal. The infection process mimics a pollen grain growing into an ovary during fertilization. Infection requires that the fungal spore have access to the stigma; consequently, plants infected by Claviceps are mainly outcrossing species with open flowers, such as rye (Secale cereale) and ryegrasses (genus Lolium). The proliferating fungal mycelium then destroys the plant ovary and connects with the vascular bundle originally intended for seed nutrition. The first stage of ergot infection manifests itself as a white soft tissue (known as sphacelia) producing sugary honeydew, which often drops out of the infected grass florets. This honeydew contains millions of asexual spores (conidia), which insects disperse to other florets. Later, the sphacelia convert into a hard dry sclerotium inside the husk of the floret. At this stage, alkaloids and lipids accumulate in the sclerotium.

Claviceps species from tropic and subtropic regions produce macro- and microconidia in their honeydew. Macroconidia differ in shape and size between the species, whereas microconidia are rather uniform, oval to globose (5×3 μm). Macroconidia are able to produce secondary conidia. A germ tube emerges from a macroconidium through the surface of a honeydew drop and a secondary conidium of an oval to pearlike shape is formed, to which the contents of the original macroconidium migrates. Secondary conidia form a white, frost-like surface on honeydew drops and spread via the wind. No such process occurs in Claviceps purpurea, Claviceps grohii, Claviceps nigricans and Claviceps zizaniae, all from northern temperate regions.

When a mature sclerotium drops to the ground, the fungus remains dormant until proper conditions (such as the onset of spring or a rain period) trigger its fruiting phase. It germinates, forming one or several fruiting bodies with heads and stipes, variously coloured (resembling a tiny mushroom). In the head, threadlike sexual spores form, which are ejected simultaneously when suitable grass hosts are flowering.

Ergot infection causes a reduction in the yield and quality of grain and hay, and if livestock eat infected grain or hay it may cause a disease called ergotism. Black and protruding sclerotia of C. purpurea are well known. However, many tropical ergots have brown or greyish sclerotia, mimicking the shape of the host seed. For this reason, the infection is often overlooked.

Insects, including flies and moths, carry conidia of Claviceps species, but it is unknown whether insects play a role in spreading the fungus from infected to healthy plants.

Evolution

Regarding the evolution of plant parasitism in the Clavicipitaceae, an amber fossil discovered in 2020 preserves a grass spikelet and an ergot-like parasitic fungus. The fossil shows that the original hosts of the Clavicipitaceae could have been grasses. The discovery also establishes a minimum time for the conceivable presence of psychotropic compounds in fungi.

Several evolutionary processes have acted to diversify the array of ergot alkaloids produced by fungi; these differences in enzyme activities are evident at the levels of substrate specificity (LpsA), product specification (EasA, CloA) or both (EasG and possibly CloA). The "old yellow enzyme", EasA, presents an outstanding example. This enzyme catalyzes reduction of the C8=C9 double-bond in chanoclavine I, but EasA isoforms differ in whether they subsequently catalyze reoxidation of C8–C9 after rotation. Ergot alkaloids have a wide range of biological activities, including effects on circulation and neurotransmission.

Ergot alkaloids are classified as:

  1. derivatives of 6,8-dimethylergoline and
  2. lysergic acid derivatives.

Ergotism is the name for sometimes severe pathological syndromes affecting humans or other animals that have ingested plant material containing ergot alkaloid, such as ergot-contaminated grains.

The Hospital Brothers of St. Anthony, an order of monks established in 1095, specialized in treating ergotism victims with balms containing tranquilizing and circulation-stimulating plant extracts. The common name for ergotism is "St. Anthony's fire",

There are two types of ergotism. The first is characterized by muscle spasms, fever and hallucinations and the victims may appear dazed, be unable to speak, become manic, or have other forms of paralysis or tremors, and suffer from hallucinations and other distorted perceptions. This is caused by serotonergic stimulation of the central nervous system by some of the alkaloids.

Klotz offers a detailed overview of the toxicities in mammalian livestock, stating that the activities are attributable to antagonism or agonism of neurotransmitters, including dopamine, serotonin and norepinephrine. He also states that the adrenergic blockage by ergopeptines (e.g., ergovaline or ergotamine) leads to potent and long-term vasoconstriction, and can result in reduced blood flow resulting in intense burning pain (St. Anthony's fire), edema, cyanosis, dry gangrene and even loss of hooves in cattle or limbs in humans. Reduced prolactin due to ergot alkaloid activity on dopamine receptors in the pituitary is also common in livestock. Reduced serum prolactin is associated with various reproductive problems in cattle, and especially in horses, including agalactia and poor conception, and late-term losses of foals and sometimes mares due to dystocia and thickened placentas.

Ergot extract has been used in pharmaceutical preparations, including ergot alkaloids in products such as Cafergot (containing caffeine and ergotamine Clinical ergotism as seen today results almost exclusively from the excessive intake of ergotamine tartrate in the treatment of migraine headache. The fungi of the genera Penicillium and Aspergillus also produce ergot alkaloids, notably some isolates of the human pathogen Aspergillus fumigatus, and have been isolated from plants in the family Convolvulaceae, of which morning glory is best known. The causative agents of most ergot poisonings are the ergot alkaloid class of fungal metabolites, though some ergot fungi produce distantly related indole-diterpene alkaloids that are tremorgenic. ergotamine. Lysergic acid is a precursor for the synthesis of LSD. Their realized and hypothesized medicinal uses have encouraged intensive research since the 1950s culminating on the one hand in development of drugs both legal (e.g., bromocriptine) and illegal (e.g., LSD), and on the other hand in extensive knowledge of the enzymes, genetics and diversity of ergot alkaloid biosynthetic pathways.

Economic impact

Ergot contamination of crops continues to have economic consequences. In the European Union, ergot in grains made for human consumption can only have 0.05% of ergot in grains and up to a maximum and selling grains with a higher percentage than that would result in fines and fees. Similar standards are held for the US and Canada. Additional costs also arise from the cleaning of grains containing ergot with it being estimated to be 2€/dt. Average contamination levels in Germany between 1995 and 2004 were relatively stable with it being at 0.11% w/w. Outbreaks have caused severe localized losses, in 1998 there was almost a total loss of rye crops in Germany. In 2005, in the US Midwest there was also a widespread amount of ergot that was reported to be found in barley crops. To reduce the risk of ergot infection found in grains, farmers have to introduce different methods such as changes in crop rotation and deeper ploughing.

The consumption of ergot alkaloids poisons our livestock, particularly grazing animals such as cows, sheep, and horses. Two different ways it could be consumed by animals are either on the tip of pasture grasses or the feed grains crops we produce to feed them. In the US, annual cow losses that are associated with tall fescue toxicosis were first seen in the 1930’s. In 1990 the estimated economic loss for the cows that were affected by this was estimated to be more than $600 million. Affected livestock have reduced weight gain, fat necrosis, reduced milk production, and reduced fertility. Another symptom that could be shown is fescue foot, which is usually seen in winter months, affected animals suffer from dry gangrene. Some of the animals, especially horses, can suffer from still-births, where foals suffer from distortions in bone structure.

History

thumb|Ergot on wheat heads

Ergotism is the earliest recorded example of mycotoxicosis, or poisoning caused by toxic molds.

Early references to ergotism date back as far as 600 BC, an Assyrian tablet referred to it as a "noxious pustule in the ear of grain." In 350 BC, the Parsees described "noxious grasses that cause pregnant women to drop the womb and die in childbed." England is noticeably absent from the historical regions affected by ergotism as its main source of food was wheat, which is resistant to ergot fungi. In 994, a massive outbreak potentially attributed to ergotism caused 40,000 deaths in the regions of Aquitaine, Limousin, Périgord and Angoumois in France.

Saint Anthony's fire and the Antonites

Saint Anthony was a 3rd Century Egyptian ascetic who lived by the Red Sea and was known for long fasting in which he confronted terrible visions and temptations sent from the Devil. The sufferers would receive ergot-free meals, wines containing vasodilating and analgesic herbs, and applications of Antonites-balsam, which was the first transdermal therapeutic system (TTS) in medical history.

  1. In a printed book of 1582, the German physician Adam Lonicer wrote, that three sclerotia of ergot, used several times a day, were used by midwives as a good remedy in case of the "uprising and pain of the womb" (auffſteigen vnd wehethumb der mutter)
  2. Joachim Camerarius the Younger wrote in 1586, that sclerotia of ergot held under the tongue, would stop bleeding

To prove that ergot is a harmless sort of grain, in 1774, the French pharmacist Antoine-Augustin Parmentier edited a letter he had received from Madame Dupile, a midwife of Chaumont-en-Vexin. She had told him that if uterine contractions were too weak in the expulsion stage of childbirth, she and her mother gave peeled ergot in an amount of the filling of a thimble dispersed in water, wine or broth. The administration of ergot was followed by a mild childbirth within 15 minutes. The French physician Jean-Baptiste Desgranges (1751–1831) published in 1818, that in 1777 he had met midwives in Lyon, who successfully treated feeble uterine contractions by administering the powder of ergot. Desgranges added this remedy to his therapeutic arsenal. From 1777 to 1804, he was successful in alleviating childbirth for more than twenty women by the administration of the powder of ergot. He never saw any side-effect of this treatment.

In the United States, in 1807 Dr. John Stearns of Saratoga County, New York wrote to a friend that he had used, over several years, a pulvis parturiens with complete success in patients with "lingering parturitation". This pulvis parturiens consisted of ergot, that he called a "spurious groth of rye". He boiled "half a drachm" (ca. 2g) of that powder in half a pint of water and gave one third every twenty minutes, till the pains commenced. In 1813, Dr. Oliver Prescott (1762–1827) of Newburyport, Massachusetts published a dissertation "on the natural history and medical effects of the secale cornutum", in which he described and analysed the experience he had gathered over five years while using ergot in cases of poor uterine action in the second stage of labour in childbirth.

In 1837, the French Codex Pharmacopee Francaise required ergot to be kept in all pharmacies.

Low to very low evidence from clinical trials suggests that prophylactic use of ergot alkaloids, administered by intravenous (IV) or intramuscular (IM) in the third stage of labor, may reduce blood loss and may reduce the risk of moderate to severe hemorrhage following delivery, however this medication may also be associated with higher blood pressure and higher pain. It is not clear if oral ergot alkaloids are beneficial or harmful as they have not been well studied. these pills contained ergotin, aloes, Black Hellebore and other substances. The efficacy and safety of these pills are unknown. The FTC deemed them unsafe and ineffective and demanded that they cease and desist selling the product. Currently, over a thousand compounds have been derived from ergot ingredients.

An article appearing in the July 23, 1881 edition of Scientific American entitled "A New Exhilarating Substance" denotes cases of euphoria upon consuming tincture of ergot of rye, particularly when mixed with phosphate of soda and sweetened water. In rainy years, it was thought rye bread exceeded 5% ergot.

British author John Grigsby contends that the presence of ergot in the stomachs of some of the so-called 'bog-bodies' (Iron Age human remains from peat bogs of northeast Europe, such as the Tollund Man) is indicative of use of Claviceps purpurea in ritual drinks in a prehistoric fertility cult akin to the Greek Eleusinian Mysteries. In his 2005 book Beowulf and Grendel, he argues that the Anglo-Saxon poem Beowulf is based on a memory of the quelling of this fertility cult by followers of Odin. He writes that Beowulf, which he translates as barley-wolf, suggests a connection to ergot which in German was known as the 'tooth of the wolf'.

Linnda R. Caporael posited in 1976 that the hysterical symptoms of young women that had spurred the Salem witch trials had been the result of consuming ergot-tainted rye. However, Nicholas P. Spanos and Jack Gottlieb, after a review of the historical and medical evidence, later disputed her conclusions. Other authors have likewise cast doubt on ergotism as the cause of the Salem witch trials.

Claviceps purpurea

Mankind has known about Claviceps purpurea for a long time, and its appearance has been linked to extremely cold winters that were followed by rainy summers.

The sclerotial stage of C. purpurea conspicuous on the heads of ryes and other such grains is known as ergot. Favorable temperatures for growth are in the range of 18–30 °C. Temperatures above 37 °C cause rapid germination of conidia. Sunlight has a chromogenic effect on the mycelium, with intense coloration. Cereal mashes and sprouted rye are suitable substrates for growth of the fungus in the laboratory.

Claviceps africana

Claviceps africana infects sorghum. In sorghum and pearl millet, ergot became a problem when growers adopted hybrid technology, which increased host susceptibility.

C. africana caused ergot disease that caused a famine in 1903–1906 in northern Cameroon, West Africa, and also occurs in eastern and southern Africa, especially Zimbabwe and South Africa. Male sterile sorghums (also referred to as A-lines) are especially susceptible to infection, as first recognized in the 1960s, and massive losses in seed yield have been noted. Infection is associated with cold night temperatures that are below 12 °C occurring two to three weeks before flowering.

Sorghum ergot caused by Claviceps africana Frederickson, Mantle and De Milliano is widespread in all sorghum-growing areas, whereas the species was formerly restricted to Africa and Asia where it was first recorded more than 90 years ago, it has been spreading rapidly and by the mid-1990s it reached Brazil, South Africa and Australia. By 1997, the disease had spread to most South American countries and the Caribbean including Mexico, and by 1997 had reached Texas in the United States.

See also

  • Medicinal uses of fungi
  • Dassel History Center & Ergot Museum: a major producer of ergot

Sources

References

  • Claviceps purpurea - Ergot Alkaloid
  • Ergot article from North Dakota State University, 2002
  • PBS Secrets of the Dead: "The Witches Curse" (concerning the Salem trials and ergot)
  • Parkinson's Drugs Can Damage Heart Valves. HealthDay. January 3, 2007.