Claviceps purpurea

Last updated

Contents

Claviceps purpurea
Claviceps purpurea.JPG
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Kingdom: Fungi
Division: Ascomycota
Class: Sordariomycetes
Order: Hypocreales
Family: Clavicipitaceae
Genus: Claviceps
Species:
C. purpurea
Binomial name
Claviceps purpurea
(Fr.) Tul. 1853
Ecological races
  • 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).

Claviceps purpurea is an ergot fungus that grows on the ears of rye and related cereal and forage plants. Consumption of grains or seeds contaminated with the survival structure of this fungus, the ergot sclerotium, can cause ergotism in humans and other mammals. [1] [2] 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.

Life cycle

Various stages in the life cycle of Claviceps purpurea Claviceps purpurea - Kohler-s Medizinal-Pflanzen-185-en.jpg
Various stages in the life cycle of Claviceps purpurea
fruiting bodies with head and stipe on Sclerotium Stroma Claviceps purpurea.JPG
fruiting bodies with head and stipe on Sclerotium

An ergot kernel called Sclerotium clavus develops when a floret of flowering grass or cereal is infected by an ascospore of C. purpurea. The infection process mimics a pollen grain growing into an ovary during fertilization. Because infection requires access of the fungal spore to the stigma, plants infected by C. purpurea are mainly outcrossing species with open flowers, such as rye ( Secale cereale ) and Alopecurus.

The proliferating fungal mycelium then destroys the plant ovary and connects with the vascular bundle originally intended for feeding the developing seed. The first stage of ergot infection manifests itself as a white soft tissue (known as Sphacelia segetum) producing sugary honeydew, which often drops out of the infected grass florets. This honeydew contains millions of asexual spores (conidia) which are dispersed to other florets by insects or rain. Later, the Sphacelia segetum convert into a hard dry Sclerotium clavus inside the husk of the floret. At this stage, alkaloids and lipids (e.g. ricinoleic acid) accumulate in the Sclerotium.

When a mature Sclerotium drops to the ground, the fungus remains dormant until proper conditions trigger its fruiting phase (onset of spring, rain period, need of fresh temperatures during winter, etc.). It germinates, forming one or several fruiting bodies with head and stipe, variously colored (resembling a tiny mushroom). In the head, threadlike sexual spores (ascospores) are formed in perithecia, which are ejected simultaneously, when suitable grass hosts are flowering. Ergot infection causes a reduction in the yield and quality of grain and hay produced, and if infected grain or hay is fed to livestock it may cause a disease called ergotism.

Polistes dorsalis , a species of social wasps, have been recorded as a vector of the spread of this particular fungus. During their foraging behavior, particles of the fungal conidia get bound to parts of this wasp's body. As P. dorsalis travels from source to source, it leaves the fungal infection behind. [3] Insects, including flies and moths, have also been shown to carry conidia of Claviceps species, but if insects play a role in spreading the fungus from infected to healthy plants is unknown. [4]

Intraspecific variations

Model of Claviceps purpurea, Botanical Museum Greifswald Modell von Claviceps purpurea (Mutterkornpilz) -Osterloh Nr. 42- -Brendel 10 g, 2- (2).jpg
Model of Claviceps purpurea, Botanical Museum Greifswald

Early scientists have observed Claviceps purpurea on other Poaceae as Secale cereale . 1855, Grandclement [5] described ergot on Triticum aestivum . During more than a century scientists aimed to describe specialized species or specialized varieties inside the species Claviceps purpurea.

Later scientists tried to determine host varieties as

Molecular biology has not confirmed this hypothesis but has distinguished three groups differing in their ecological specificity. [6]

Morphological criteria to distinguish different groups: The shape and the size of sclerotia are not good indicators because they strongly depend on the size and shape of the host floret. The size of conidia can be an indication but it is weak and it is necessary to pay attention to that, due to osmotic pressure, it varies significantly if the spores are observed in honeydew or in water. The sclerotial density can be used as the groups G2 and G3 float in water.

The compound of alkaloids is also used to differentiate the strains.

Host range

Sclerotium of Claviceps purpurea on Alopecurus myosuroides Alopecurus claviceps 2.JPG
Sclerotium of Claviceps purpurea on Alopecurus myosuroides

Pooideae

Agrostis canina , Alopecurus myosuroides (G2), Alopecurus arundinaceus (G2), Alopecurus pratensis , Bromus arvensis , Bromus commutatus , Bromus hordeaceus (G2), Bromus inermis , [7] Bromus marginatus , Elymus tsukushiense , Festuca arundinacea , [8] Elymus repens (G1), Nardus stricta , Poa annua (G2), Phleum pratense , Phalaris arundinacea (G2), Poa pratensis (G1), Stipa .

Arundinoideae

Danthonia , Molinia caerulea .

Chloridoideae

Spartina , Distichlis (G3)

Panicoideae

Setaria

Epidemiology

Claviceps purpurea has been known to humankind for a long time, and its appearance has been linked to extremely cold winters that were followed by rainy springs.[ citation needed ]

The sclerotial stage of C. purpurea conspicuous on the heads of ryes and other such grains is known as ergot. Sclerotia germinate in spring after a period of low temperature. A temperature of 0-5 °C for at least 25 days is required. Water before the cold period is also necessary. [9] Favorable temperatures for stroma production are in the range of 10-25 °C. [10] Favorable temperatures for mycelial growth are in the range of 20-30 °C with an optimum at 25 °C. [10]

Sunlight has a chromogenic effect on the mycelium with intense coloration. [11]

Effects

Ergot-derived drug to stop postnatal bleeding Moederkoornpreparaat Methergin.jpg
Ergot-derived drug to stop postnatal bleeding

The disease cycle of the ergot fungus was first described in 1853, [12] but the connection with ergot and epidemics among people and animals was reported already in a scientific text in 1676. [13] The ergot sclerotium contains high concentrations (up to 2% of dry mass) of the alkaloid ergotamine, a complex molecule consisting of a tripeptide-derived cyclol-lactam ring connected via amide linkage to a lysergic acid (ergoline) moiety, and other alkaloids of the ergoline group that are biosynthesized by the fungus. [14] Ergot alkaloids have a wide range of biological activities including effects on circulation and neurotransmission. [15]

Ergotism is the name for sometimes severe pathological syndromes affecting humans or animals that have ingested ergot alkaloid-containing plant material, such as ergot-contaminated grains. Monks of the order of St. Anthony the Great specialized in treating ergotism victims [16] with balms containing tranquilizing and circulation-stimulating plant extracts; they were also skilled in amputations.[ citation needed ] The common name for ergotism is "St. Anthony's Fire", [16] in reference to monks who cared for victims as well as symptoms, such as severe burning sensations in the limbs. [17] These are caused by effects of ergot alkaloids on the vascular system due to vasoconstriction of blood vessels, sometimes leading to gangrene and loss of limbs due to severely restricted blood circulation.

The neurotropic activities of the ergot alkaloids may also cause hallucinations and attendant irrational behaviour, convulsions, and even death. [14] [15] Other symptoms include strong uterine contractions, nausea, seizures, and unconsciousness. Since the Middle Ages, controlled doses of ergot were used to induce abortions and to stop maternal bleeding after childbirth. [18] Ergot alkaloids are also used in products such as Cafergot (containing caffeine and ergotamine [18] or ergoline) to treat migraine headaches. Ergot extract is no longer used as a pharmaceutical preparation.[ citation needed ]

Ergot contains no lysergic acid diethylamide (LSD) but rather ergotamine, which is used to synthesize lysergic acid, an analog of and precursor for synthesis of LSD. Moreover, ergot sclerotia naturally contain some amounts of lysergic acid. [19]

Culture

Sphacelia segetum on potato dextrose agar Sphacelia Segetum.JPG
Sphacelia segetum on potato dextrose agar

Potato dextrose agar, wheat seeds or oat flour are suitable substrates for growth of the fungus in the laboratory. [20]

Agricultural production of Claviceps purpurea on rye is used to produce ergot alkaloids.[ citation needed ] Biological production of ergot alkaloids is also carried out by saprophytic cultivations.

Speculations

During the Middle Ages, human poisoning due to the consumption of rye bread made from ergot-infected grain was common in Europe. These epidemics were known as Saint Anthony's fire, [16] or ignis sacer.

Gordon Wasson proposed that the psychedelic effects were the explanation behind the festival of Demeter at the Eleusinian Mysteries, where the initiates drank kykeon . [21]

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. [22] However, her conclusions were later disputed by Nicholas P. Spanos and Jack Gottlieb, after a review of the historical and medical evidence. [23] Other authors have likewise cast doubt on ergotism having been the cause of the Salem witch trials. [24]

The Great Fear in France during the Revolution has also been linked by some historians to the influence of ergot.[ citation needed ]

British author John Grigsby claims that the presence of ergot in the stomachs of some of the so-called 'bog-bodies' (Iron Age human remains from peat bogs N E Europe such as Tollund Man), reveals that ergot was once a ritual drink in a prehistoric fertility cult akin to the Eleusinian Mysteries cult of ancient Greece. In his 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 states that Beowulf, which he translates as barley-wolf, suggests a connection to ergot which in German was known as the 'tooth of the wolf'.[ citation needed ]

An outbreak of violent hallucinations among hundreds of residents of Pont St. Esprit in 1951 in the south of France has also been attributed to ergotism. [25] Shortly after the event at least four people had been declared dead, [25] although some claim the total number of deaths to be five or seven. [26]

See also

Related Research Articles

<span class="mw-page-title-main">Ergot</span> Group of fungi of the genus Claviceps

Ergot or ergot fungi refers to a group of fungi of the genus Claviceps.

<span class="mw-page-title-main">Ergotism</span> Effect of long-term ergot poisoning

Ergotism is the effect of long-term ergot poisoning, traditionally due to the ingestion of the alkaloids produced by the Claviceps purpurea fungus—from the Latin clava "club" or clavus "nail" and -ceps for "head", i.e. the purple club-headed fungus—that infects rye and other cereals, and more recently by the action of a number of ergoline-based drugs. It is also known as ergotoxicosis, ergot poisoning, and Saint Anthony's fire.

<span class="mw-page-title-main">Ergine</span> Chemical compound

Ergine, also known as d-lysergic acid amide (LSA) and d-lysergamide, is an ergoline alkaloid that occurs in various species of vines of the Convolvulaceae and some species of fungi. The psychedelic properties in the seeds of ololiuhqui, Hawaiian baby woodrose and morning glories have been linked to ergine and/or isoergine, its epimer, as it is an alkaloid present in the seeds.

<span class="mw-page-title-main">Ergoline</span> Chemical compound

Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.

<span class="mw-page-title-main">Ergotamine</span> Chemical compound in the ergot family of alkaloids

Ergotamine, sold under the brand names Cafergot and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor.

<span class="mw-page-title-main">Lysergic acid hydroxyethylamide</span> Chemical compound

D-Lysergic acid α-hydroxyethylamide, also known as D-lysergic acid methyl carbinolamide, is a Lysergamide and alkaloid of the Ergoline family, it is present in higher concentrations in the parasitic fungi species "Claviceps", mainly the Claviceps paspali, also in Claviceps Purpurea. This fungi grows in various species in the Convolvulaceae family like the Ipomoea violacea, the Rivea corymbosa (Ololiuhqui), and the Argyreia nervosa. Heavenly Blue Morning Glory and Hawaiian Baby Woodrose especially contain high amounts of LSH, with content varying between species and by how fresh the seeds are. LSH is a psychoactive Ergoline and has effects similar to LSD due to similarity in the structure and is the main psychoactive compound found in Claviceps Paspali and in (fresh) Heavenly Blue Morning Glory Seeds. LSH is unstable and breaks down into LSA quickly, so old seeds often only contains LSA and iso-LSA. When the seeds are fresh, they contain significantly higher amounts of LSH.

<span class="mw-page-title-main">Methylergometrine</span> Chemical compound

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.

<span class="mw-page-title-main">Sclerotium</span> Mycelial mass

A sclerotium, is a compact mass of hardened fungal mycelium containing food reserves. One role of sclerotia is to survive environmental extremes. In some higher fungi such as ergot, sclerotia become detached and remain dormant until favorable growth conditions return. Sclerotia initially were mistaken for individual organisms and described as separate species until Louis René Tulasne proved in 1853 that sclerotia are only a stage in the life cycle of some fungi. Further investigation showed that this stage appears in many fungi belonging to many diverse groups. Sclerotia are important in the understanding of the life cycle and reproduction of fungi, as a food source, as medicine, and in agricultural blight management.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

<span class="mw-page-title-main">Clavicipitaceae</span> Family of fungi

The Clavicipitaceae are a family of fungi within the order Hypocreales. A 2008 estimate placed 43 genera in the family, but a study in 2020 has increased this number to 50.

<i>Epichloë</i> Genus of fungi

Epichloë is a genus of ascomycete fungi forming an endophytic symbiosis with grasses. Grass choke disease is a symptom in grasses induced by some Epichloë species, which form spore-bearing mats (stromata) on tillers and suppress the development of their host plant's inflorescence. For most of their life cycle however, Epichloë grow in the intercellular space of stems, leaves, inflorescences, and seeds of the grass plant without incurring symptoms of disease. In fact, they provide several benefits to their host, including the production of different herbivore-deterring alkaloids, increased stress resistance, and growth promotion.

<i>Claviceps sorghi</i> Species of fungus

Claviceps sorghi is a fungal plant pathogen belonging to the phylum Ascomycota in the kingdom Fungi- its anamorphic phase is known as sphacelia sorghi. This species was first found in In India in 1915 and officially recorded in 1948 . The Claviceps genus is known for their infection of cereal and millet crops. This particular species of Claviceps infects Sorghum- giving the fungus its name 'sorghi'. These species in Claviceps are known to produce ergot on their host, as a byproduct of their infection. This can cause the disease known as ergotism when the infected crop is consumed.

<i>Ustilaginoidea virens</i> Species of fungus

Ustilaginoidea virens, perfect sexual stage Villosiclava virens, is a plant pathogen which causes the disease "false smut" of rice which reduces both grain yield and grain quality. The disease occurs in more than 40 countries, especially in the rice producing countries of Asia. but also in the U.S. As the common name suggests, it is not a true smut (fungus), but an ascomycete. False smut does not replace all or part of the kernel with a mass of black spores, rather sori form erupting through the palea and lemma forming a ball of mycelia, the outermost layers are spore-producing. Infected rice kernels are always destroyed by the disease.

Magnaporthe salvinii is a fungus known to attack a variety of grass and rice species, including Oryza sativa and Zizania aquatica. Symptoms of fungal infection in plants include small, black, lesions on the leaves that develop into more widespread leaf rot, which then spreads to the stem and causes breakage. As part of its life cycle, the fungus produces sclerotia that persist in dead plant tissue and the soil. Management of the fungus may be effected by tilling the soil, reducing its nitrogen content, or by open field burning, all of which reduce the number of sclerotia, or by the application of a fungicide.

<i>Lolium arundinaceum</i> Species of flowering plant

Lolium arundinaceum, tall fescue is a cool-season perennial C3 species of grass that is native to Europe. It occurs on woodland margins, in grassland and in coastal marshes. It is also an important forage grass with many cultivars that used in agriculture and is used as an ornamental grass in gardens, and sometimes as a phytoremediation plant.

<span class="mw-page-title-main">Ergocryptine</span> Chemical compound

Ergocryptine is an ergopeptine and one of the ergoline alkaloids. It is isolated from ergot or fermentation broth and it serves as starting material for the production of bromocriptine. Two isomers of ergocryptine exist, α-ergocryptine and β-ergocryptine. The beta differs from the alpha form only in the position of a single methyl group, which is a consequence of the biosynthesis in which the proteinogenic amino acid leucine is replaced by isoleucine. β-Ergocryptine was first identified in 1967 by Albert Hofmann. Ergot from different sources have different ratios of the two isomers.

<span class="mw-page-title-main">Plant use of endophytic fungi in defense</span>

Plant use of endophytic fungi in defense occurs when endophytic fungi, which live symbiotically with the majority of plants by entering their cells, are utilized as an indirect defense against herbivores. In exchange for carbohydrate energy resources, the fungus provides benefits to the plant which can include increased water or nutrient uptake and protection from phytophagous insects, birds or mammals. Once associated, the fungi alter nutrient content of the plant and enhance or begin production of secondary metabolites. The change in chemical composition acts to deter herbivory by insects, grazing by ungulates and/or oviposition by adult insects. Endophyte-mediated defense can also be effective against pathogens and non-herbivory damage.

Many species of fungi produce secondary metabolites called mycotoxins. These toxins can be very detrimental to both humans and animals. The side-effects of ingesting these toxic substances are called mycotoxicosis, which can be a variety of medical conditions. The most common fungi that produce mycotoxins include Fusarium, Aspergillus, and Penicillium.

<span class="mw-page-title-main">Secalonic acid</span> Group of chemical compounds

Secalonic acids are a group of xanthone derivatives closely related to ergoflavin and ergochrysin A that are collectively called ergochromes and belong to a class of mycotoxins initially isolated as major ergot pigments from the fungi Claviceps purpurea that grows parasitically on rye grasses. From early times and particularly in medieval Europe the consumption of grains containing ergot has repeatedly lead to mass poisonings known as ergotism which was caused by toxic ergot alkaloids and mycotoxins such as the ergochromes, due to contamination of flour by C. purpurea. A cluster of genes responsible for the synthesis of secalonic acids in C. purpurea has been identified. Secalonic acid D the enantiomer of secalonic acid A is a major environmental toxin, isolated from the fungus Penicillium oxalicum, and is a major microbial contaminant of freshly-harvested corn which causes toxicity through contamination of foodstuffs.

Claviceps pusilla, also known as bluestem ergot, is a parasitic fungus primarily of the grass tribe Angropogoneae, particularly those in the tribe referred to as "bluestem". C. pusilla occasionally manifests characteristic triangular conidia which appear to be unique among Claviceps species.

References

  1. "ergot definition". mondofacto. Archived from the original on 2016-03-03.
  2. "ergot". Dorland's Medical Dictionary. Archived from the original on September 10, 2009. Retrieved August 9, 2017 via Merck Source.
  3. Hardy, Tad N. (September 1988). "Gathering of Fungal Honeydew by Polistes spp. (Hymenoptera: Vespidae) and Potential Transmission of the Causal Ergot Fungus". The Florida Entomologist. 71 (3): 374–376. doi:10.2307/3495447. JSTOR   3495447.
  4. Butler, M.D.; Alderman, S. C.; Hammond, P.C.; Berry, R. E. (2001). "Association of Insects and Ergot (Claviceps purpurea) in Kentucky Bluegrass Seed Production Fields". J. Econ. Entomol. 94 (6): 1471–1476. doi: 10.1603/0022-0493-94.6.1471 . PMID   11777051. S2CID   8725020.
  5. Mr Gonod d'Artemare (1860). "Note sur l'ergot du froment". Bulletin de la Société botanique de France : 771.
  6. Pažoutová S.; Olšovská J.; Linka M.; Kolínská R.; Flieger M. (2000). "Chemoraces and habitat specialization of Claviceps purpurea populations". Applied and Environmental Microbiology. 66 (12): 5419–5425. Bibcode:2000ApEnM..66.5419P. doi:10.1128/aem.66.12.5419-5425.2000. PMC   92477 . PMID   11097923.
  7. Eken C.; Pažoutová S.; Honzátko A.; Yildiz S. (2006). "First report of Alopecurus arundinaceus, A. myosuroides, Hordeum violaceum and Phleum pratense as hosts of Claviceps purpurea population G2 in Turkey". J. Plant Pathol. 88: 121.
  8. Douhan G. W.; Smith M. E.; Huyrn, K. L.; Yildiz S. (2008). "Multigene analysis suggests ecological speciation in the fungal pathogen Claviceps purpurea". Molecular Ecology. 17 (9): 2276–2286. Bibcode:2008MolEc..17.2276D. doi:10.1111/j.1365-294X.2008.03753.x. PMC   2443689 . PMID   18373531.
  9. Kichhoff H (1929). "Beiträge zur Biologie und Physiologie des Mutterkornpilzes". Centralblat. Bakteriol. Parasitenk. Abt. II. 77: 310–369.
  10. 1 2 Mitchell D.T. (1968). "Some effects of temperature on germination of sclerotia in Claviceps purpurea". Trans. Br. Mycol. Soc. 51 (5): 721–729. doi:10.1016/s0007-1536(68)80092-0.
  11. McCrea A (1931). "The reactions of Claviceps purpurea to variations of environment" (PDF). Am. J. Bot. 18 (1): 50–78. doi:10.2307/2435724. hdl: 2027.42/141053 . JSTOR   2435724.
  12. Tulasne, L.-R. (1853) Mémoire sur l'ergot des glumacéses Ann. Sci. Nat. (Parie Botanique), 20 5-56
  13. Dodart D. (1676) Le journal des savans, T. IV, p. 79
  14. 1 2 Tudzynski P, Correia T, Keller U (2001). "Biotechnology and genetics of ergot alkaloids". Appl Microbiol Biotechnol. 57 (5–6): 4593–4605. doi:10.1007/s002530100801. PMID   11778866. S2CID   847027.
  15. 1 2 Eadie MJ (2003). "Convulsive ergotism: epidemics of the serotonin syndrome?". Lancet Neurol. 2 (7): 429–434. doi:10.1016/S1474-4422(03)00439-3. PMID   12849122. S2CID   12158282.
  16. 1 2 3 J. Heritage; Emlyn Glyn Vaughn Evans; R. A. Killington (1999). Microbiology in Action . Cambridge University Press. p.  115.
  17. St. Anthony's Fire -- Ergotism
  18. 1 2 Untersuchungen über das Verhalten der Secalealkaloide bei der Herstellung von Mutterkornextrakten. Labib Farid Nuar. Universität Wien - 1946 - (University of Vienna)
  19. Correia T, Grammel N, Ortel I, Keller U, Tudzynski P (2001). "Molecular cloning and analysis of the ergopeptine assembly system in the ergot fungus Claviceps purpurea". Chem. Biol. 10 (12): 1281–1292. doi: 10.1016/j.chembiol.2003.11.013 . PMID   14700635.
  20. Mirdita, Vilson (2006). Genetische Variation für Resistenz gegen Mutterkorn (Claviceps purpurea [Fr.] Tul.) bei selbstinkompatiblen und selbstfertilen Roggenpopulationen (Thesis). Archived from the original on 2009-09-09. Retrieved 2009-04-25.
  21. Gordon Wasson, The Road To Eleusis: Unveiling The Secret of The Mysteries (New York: Harcourt Brace Jovanovich, 1977) ISBN   0151778728
  22. Caporael LR (April 1976). "Ergotism: the satan loosed in Salem?". Science. 192 (4234): 21–6. Bibcode:1976Sci...192...21C. doi:10.1126/science.769159. PMID   769159. Archived from the original on 2008-05-11. Retrieved 2009-04-25.
  23. Spanos NP, Gottlieb J (December 1976). "Ergotism and the Salem Village witch trials". Science. 194 (4272): 1390–4. Bibcode:1976Sci...194.1390S. doi:10.1126/science.795029. PMID   795029.
  24. Woolf A (2000). "Witchcraft or mycotoxin? The Salem witch trials". J Toxicol Clin Toxicol. 38 (4): 457–460. doi:10.1081/CLT-100100958. PMID   10930065. S2CID   10469595.
  25. 1 2 Gabbai, J.; Lisbonne, L. & Pourquier, F. (September 1951). "Ergot poisoning at Pont St. Esprit". Br Med J. 15 (4732): 2276–2286. doi:10.1136/bmj.2.4732.650. PMC   2069953 . PMID   14869677.
  26. "Talk: "Cursed Bread: the Sinuous Story of a Mass Poisoning by Bread in Southern France in 1951," by Steven Kaplan, Cornell University". liberalarts.utexas.edu. Retrieved 2024-01-30.