Lecture 6 Mycotoxicosis And Mycetisms PDF

oxigenic and Poisonous Fungi Biology General Medicine Lecture № 6  Toxins of Fungi Many fungi can produce compounds toxic to other organisms. All of them are their secondary metabolites Mycotoxins - toxic to ani...

oxigenic and Poisonous Fungi Biology General Medicine Lecture № 6  Toxins of Fungi Many fungi can produce compounds toxic to other organisms. All of them are their secondary metabolites Mycotoxins - toxic to animals, humans and plants Secondary metabolites :  they tend to be produced at the end of the exponential growth phase in batch culture or when growth is substrate-limited in continuous culture;  they are produced from common metabolic intermediates but by special enzymatic pathways encoded by specific genes;  they are not essential for growth or normal metabolism;  their production tends to be genus-, species- or even strain-specific.  Toxins of Fungi Fungal poisoning caused by mycotoxins is of two main ways. 1) ‘mycotoxicosis’, i.e. poisoning by toxins of microscopic fungi (micromycetes), which develop on grain and other food products, as well as on feed of farm animals, as a result of which they acquire toxic properties. 2) ‘mycetism’ is intoxication caused by eating fruiting bodies of mushrooms (macromycetes) in view of their incorrect identification during harvest (due to the similarity with edible fungi). The main differences between these forms of poisoning: 1) Nature of toxins and location at the time of poisoning: Exotoxins Endotoxins 2) By descent from various producer fungi (micro- and macromycetes)  Mycotoxicosis. Toxigenic Fungi Over 400 different mycotoxin metabolites have been identified.  non-protein substances (heterocyclic compounds, aliphatic hydrocarbons, indole alkaloids).  have low molecular weight (less than 1000 daltons)  difficult for detection. They are invisible and tasteless.  difficult to mitigate. Mycotoxins are very stable and are hardly destroyed by processing or boiling of food  problematic due to their chronic effects. Even in low concentration they have carcinogenic, mutagenic, teratogenic, and immuno-, hepato-, nephro-, and neurotoxic properties  They are potent cell poisons Mycotoxicology - the status of an independent science was obtained after the discovery of aflatoxins (1960) Food Agriculture Organisation: approximately 25 % of the global food and feed crop output is affected by mycotoxins. mycotoxin-contaminated foods - main issue in food safety worldwide  Mycotoxicosis. Toxigenic Fungi The mycotoxin contamination of crops is generally regulated by two main factors: susceptibility of the host plant, the geographic and climatic conditions. There are more than 300 toxigenic species. These fungi can be configured into 2 groups: Field Fungi (e.g. Claviceps, Fusrium) produce mycotoxins on the plants before the harvest due to toxigenic fungal contamination in the field. Storage Fungi (e.g. Aspergillius, Penicillium) produce mycotoxins at the postharvest stage, encompassing stages of the food chain (i.e., storage, processing, and transportation). Ways: nutritionally (when eating food) through the skin and mucous membranes of the respiratory tract. The principles in the classification of mycotoxicoses: 1) The genus and / or species name of the toxigenic fungus (aspergillofumigatotoxicosis, etc.) 2) The name of the toxin (ergotism, aflatoxicosis, etc.) 3) Clinic or symptoms of illness - “drunk bread”, septic tonsillitis (now rarely used)  Field Fungi: Claviceps purpurea Taxonomy: Family Clavicipitaceae, Order Hypocreales, Class Sordariomycetes, Phylum Ascomycota, Kingdom Fungi. There are over 40 species of Claviceps, all of which are parasitic on grasses, rushes and, occasionally, sedges. The best known species is C. purpurea, the cause of ergot of grasses and cereals. Other economically important species are C. sorghi and C. africana which cause ergot of sorghum. Habitat and distribution. Claviceps purpurea occurs in temperate regions and has an exceptionally wide host range for a biotrophic pathogen. Most commonly affected grains: rye, wheat and barley. It affects oats only rarely. ergot Ergot is the French name for a cock’s spur  Field Fungi: Claviceps purpurea Life cycle of Claviceps Honeydew exudes from infected florets  Field Fungi: Claviceps purpurea Sprouted sclerotia with capitate stroma Ergots (sclerotia) in place of the grains of a plant Longitudinal section through the stroma Perithecia with asci and ascospores  Field Fungi: Claviceps purpurea Toxins 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 (7) of the ergoline group Ergot alkaloid Do not destroy during heat treatment! Bread is toxic!  Field Fungi: Claviceps purpurea Clinical Toxicology. Ergotism is the name of disease of humans or animals that have ingested ergot alkaloid-containing plant material, such as ergot-contaminated grains.  Field Fungi: Claviceps purpurea Gangrenous ergotism, ergot alkaloids affect on the vascular system due to vasoconstriction of blood vessels, sometimes leading to gangrene and loss of limbs due to severely restricted blood circulation Convulsive ergotism, the nervous system is affected (hallucinations, attendant irrational behaviour, convulsions, and even death). Other symptoms include strong uterine, contractions, nausea, seizures and and unconsciousness. "Witte Dance" Field Fungi: Claviceps purpurea Monks of the order of St. Anthony the Great specialized in treating ergotism victims with balms containing tranquilizing and circulation-stimulating plant extracts; they were also skilled in amputations. The common name for ergotism is "St. Anthony's Fire", in reference to monks who cared for victims as well as symptoms, such as severe burning sensations in the limbs.  Field Fungi: Claviceps purpurea The ergot alkaloids have some important medical uses, to relieve some types of migraine and to control hemorrhaging after childbirth. They can also be abused – the indole nucleus of one of the ergot alkaloids, ergotamine, is lysergic acid, and this can be altered chemically to produce the hallucinogenic drug, LSD. Dr. Albert Hofmann  Field Fungi: Claviceps purpurea Syd Barrett, 1968 and 1975. Between the two photographs lies a time gap of only 7 years. The fate of the genius rocker and founder of the British Pink Floyd band, Syd Barrett, is indicative. Being carried away by LSD, he soon began to suffer from severe depression, left the group and left London. A rare clinical case of ergotism after taking LSD (2011)  Field Fungi: Fusarium graminearum Taxonomy: Family Nectriaceae, Order Hypocreales, Class Sordariomycetes, Phylum Ascomycota, Kingdom Fungi. Anamorph: Fusarium graminearum Teleomorph was described as Gibberella zeae The genus Fusarium includes numerous (70) toxigenic species that are pathogenic to plants or humans, and are able to colonize a wide range of environments on earth. Fusarium graminearum Schwabe is the most economically important toxigenic species in the genus Habitat and distribution. Cosmopolitan in soils from the permafrost of the Arctic to sand in the Sahara desert. They are associated with a wide range of plant diseases: head blight of wheat, barley, and oats, and maize ear rot  Field Fungi: Fusarium graminearum Morphology. Fusarium graminearum is characterized by long, narrow macroconidia that are 5- to 6-septate and straight or slightly curved; no microconidia are produced, and chlamydospores occur in the mycelium or in conidia, but they are not common. Colonies on PDA (potato dextrose agar) usually produce a red pigment in the undersurface, and aerial mycelium is white to tan or pink. Blue-black perithecia may form  Field Fungi: Fusarium graminearum Toxins. The infected seed can be a source of mycotoxins such as zearalenone, fumonisin, trichothecenes and vomitoxin (deoxynivalenol (DON))  Crops: Wheat and maize, asparagus, figs, forage Zearalenone, an oestrogenic grasses, soybean and other legumes, spice plants hormone causes vulvovaginitis and and medicinal plants, and some nut crops such as infertility in cattle and pigs, pistachio. Also can occur in spoiled food (infected plants)  The wheat with an infected grain content of more than 5% cannot be used as food for Fumonisins cause fatal livestock diseases and humans and animals, since the content of are considered potentially carcinogenic mycotoxins in it exceeds the permissible. mycotoxins for humans.   Eating bread made from containing grains causes mycotoxicosis called “drunk bread”, Trichothecenes are potent inhibitors of protein since poisoning is accompanied by dizziness, synthesis. Cause toxic aleukia (reduction in vomiting and other symptoms resembling white blood cell count) in farm animals and severe alcohol poisoning. humans and also septic tonsillitis  Storage Fungi: Aspergillus flavus Taxonomy: Family Nectriaceae, Order Hypocreales, Class Sordariomycetes, Phylum Ascomycota, Kingdom Fungi. Teleomorph: Petromyces flavus, Anamorph: Aspergillus flavus. The genus Aspergillus is among the economically most important fungal genera, which contains about 350 species. Widespread geographically They are major food spoilage organisms, growing on stored cereals, spices, peanut, nuts, bread, dried and cured ham, pickles, jams and preserves. Colonization of food and feedstuff can result in its contamination by serious mycotoxins.  Storage Fungi: Aspergillus flavus Colonies typically spread slowly but quickly assume a greenish-blue pigmentation due to abundant conidium formation. The pigmentation of mature conidia is at least partly due to melanin. The conidial state is more commonly observed. The conidial states are generally phialidic. The conidiophore tip is swollen into a hemispherical or club-shaped structure. Conidiophore may be uniseriate or biseriate (sterile cells (metulae) is formed by the vesicle, and on it – phialides) The teleomorph gymnothecium or clestothecium.  Storage Fungi: Aspergillus flavus Toxins. the most important are aflatoxins (B1, B2, G1, G2, M1), ochratoxin A, and fumonisins Aflatoxins heterocyclic compounds A.Flavus = aflatoxin (aflatoxins are produced mainly by Aspergillus flavus (hence the name aflatoxin)) There are nearly 16 types of aflatoxins (mainly of them - B1, B2, G1, G2 , M1). Contaminate corn, soybeans, peanuts, meet in the milk Aflatoxin B1 – are the most toxic and carcinogenic naturally occurring mycotoxins Primary liver cancer in humans is possible when aflatoxin is ingested regularly with food at a dose of 500 mcg per 1 kg of body weight.  Storage Fungi: Aspergillus flavus Ochratoxins A, B, C (produce by Aspergillus ochraceus) a potent pentaketide nephrotoxin distributed in food and feed products ( grains , legumes, coffee, dried fruits , beer and wine, and meats)  Inhibit protein synthesis and glycogen metabolism  Cause degradation and fibrosis of the kidneys and liver  Have neurotoxic, teratogenic, embryotoxic, carcinogenic and immunosuppressive effects. Poisonous Fungi. Mycetism  Poisonous Fungi. Mycetism  Mushroom poisoning is a significant and increasing form of toxin-induced-disease.  Among poisoning of plant origin, mushrooms poisoning occupy a leading place (approximate 50–100 deaths/year in Europe ). Poisonous mushrooms are sometimes called toadstools. Some toadstools contain deadly toxins, the classic examples being the “death cap” Amanita phalloides (phallotoxins), and the “destroying angel” Amanita virosa. (amatoxins). They are not normally classed as mycotoxins.  Poisonous Fungi. Mycetism Agaricus Macromycetes: edible inedible (do not contain toxic substances, but have an unpleasant odor, a bitter or pungent taste) Tylopilus felleus conditionally edible (contain toxic or highly irritating substances, which, however, are destroyed or removed by appropriate treatment) poisonous Gyromitra Amanita  Poisonous Fungi. Mycetism Сlassifications of mushroom poisoning Group 1 - Cytotoxic mushroom poisoning. Syndromes with specific major internal organ pathology (e.g. amatoxins); Group 2 - Neurotoxic mushroom poisoning. Syndromes with primary neurotoxicity (e.g. psilocybins and related toxins, muscarines). Group 3 - Myotoxic mushroom poisoning. Syndromes with rhabdomyolysis as the primary feature. Group 4 – Metabolic, endocrine and related toxicity mushroom poisoning. Syndromes with a variety of clinical presentations affecting metabolic and/or endocrine processes (e.g. gyromitrins, coprines). Group 5 - Gastrointestinal irritant mushroom poisoning. This group includes a wide variety of mushrooms that cause gastrointestinal effects without causing other clinically significant effects. Group 6 - Miscellaneous adverse reactions to mushrooms. Syndromes which do not fit within the previous 5 groups: (shiitake mushroom dermatitis and others).  Conditionally edible mushrooms : Gyromitra esculenta Taxonomy: Family Helvellaceae, Order Pezizales, Class Pezizomycetes, Phylum Ascomycota, Kingdom Fungi. It is harvested and eaten by many people in northern Europe and also in the USA, although it is poisonous, even fatal, unless properly dried and boiled. Morphology. Resembling a brain, the irregularly shaped cap, wrinkled as it grows and ages. The cap color may be various shades of reddish-, chestnut-, purplish-, bay-, dark or sometimes golden-brown. Gyromitra esculenta has a solid stipe whereas those of true morels (Morchella spp.) are hollow. The smell can be pleasant and has been described as fruity, and the fungus is mild-tasting. The spore print is whitish, with transparent spores that are elliptical and 17–22 μm in length. Habitat and distribution. In the spring, at the end of April - May, massively developing on sandy soil in pine forests. Group 4 – Metabolic, endocrine and related toxicity mushroom poisoning  Gyromitra esculenta – Строчок обыкновенный Toxin: Gyromitrin - acetaldehyde N-methyl N-formyl hydrazone. It is a direct irritant to the gastrointestinal tract. In stomach gyromitrin hydrolysis to monomethylhydrazine (more dangerous) It is carcinogen and can oxidative damage to the red blood cells. Cooking must be performed in an open vessel to allow Gyromitrin is extremely volatile methylhydrazine to escape; otherwise, poisoning can occur. Clinical Toxicology. Symptoms do not begin until a 6-8 hours after consumption. The symptoms of poisoning are typically gastrointestinal and neurological. These include:  Vomiting, nausea, stomach crams, etc.  Bloating feeling, faintness, loss of muscular control and fever  Most instance victim makes full recovery  In rare instance can cause death (2-4% of mushrooms fatalities). Victim consumes large amount.  Poisonous Fungi: Coprinopsis atramentaria Taxonomy: Family Psathyrellaceae, Order Agaricales, Class Basidiomycetes, Phylum Basidiomycota, Kingdom Fungi.  ‘ink-caps’ mushrooms with deliquescent inaequi- hymenial gills undergoing autodigestion at maturity.  edible mushrooms, sometimes they are poisonous when consumed with alcohol – hence another common name, tippler's bane. Morphology. Basidiocarps have greyish or brownish-grey cap (bell-shaped, then splits). The flesh is thin and pale grey in color. Spore development and discharge occurs first at the base of the gill, followed by autodigestion of the discharged basidia and the hyphae which supported them. The digested tissue drips away from the base of the gills as a black fluid which can be used as writing ink. Habitat. Buried wood, grassland, meadows, disturbed ground, and open terrain from late spring to autumn Group 4 – Metabolic, endocrine and related toxicity mushroom poisoning  Poisonous Fungi: Coprinopsis atramentaria Toxins The fungus contains a cyclopropylglutamine compound called coprine. It blocks the action of an enzyme, acetaldehyde dehydrogenase, which breaks down acetaldehyde in the body. Acetaldehyde is an intermediate metabolite of ethanol and is responsible for most symptoms of a hangover; its effect on autonomic β receptors is responsible for the vasomotor symptoms. ethanol acetaldehyde Clinical Toxicology Symptoms may occur within 30-60 minutes acetaldehyde after consumption of mushroom. If alcoholic dehydrogenase beverages have been consumed. Causes antabuse-like reaction ("disulfiram coprine. syndrome"): Nausea, vomiting and cramps Hot flushes on face and neck, metallic taste, numbness in hand Symptoms continue as long as alcohol is still in system. Toxin may last up to 72 hours.  Poisonous Fungi: Аmanita phalloides Taxonomy: Family Amanitaceae, Order Agaricales, Class Basidiomycetes, Phylum Basidiomycota, Kingdom Fungi. Morphology. Basidiocarp has cap, initially rounded and hemispherical, but flattening with age. The colour of the cap is pale- or olive-green. The remains of the partial veil are seen as a skirtlike. The white gills are free. The stipe is white with sac-like white volva (base). As the volva (may be hidden by leaf) is a diagnostic feature, it is important to remove some debris to check for it. Young basidiocarps are covered by a universal veil and resemble the eggs, which then breaks, leaving the volva as a remains. Volva – the remains of universal veil  Poisonous Fungi: Аmanita phalloides Habitat and distribution The death cap is native to Europe. also in Morocco and Algeria in north Africa. In west Asia it has been reported from forests of northern Iran. It is symbiotic with several trees (mainly with oaks). Amanita phalloides, also known as ‘death cap’, is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. In view of the possible confusion between edible and poisonous species, it is obviously best to avoid eating basidiocarps of any whose identity is uncertain. Group 1 - Cytotoxic mushroom poisoning There are also species whose basidiocarps are excellent to eat, most notably A. caesarea (Caesar’s mushroom), which has been hunted enthusiastically in Southern European countries since Roman times. Other edible species are A. rubescens (blusher), A. vaginata (grisette) and A. fulva (tawny grisette)  Poisonous Fungi: Аmanita phalloides Toxins amatoxins, phallotoxins, and virotoxins - Cyclopeptides. α-amanitin is the main responsible for the Phalloidins are toxic to liver cells, they have toxic effects in humans. since been found to add little to the death cap's α-amanitin inhibits RNA polymerase II, toxicity, as they are not absorbed through the causing protein deficit and ultimately cell gut. death Phallolysins show hemolytic (red blood cell– the liver is the main target organ of destroying) activity in vitro. toxicity, but other organs are also Virotoxins do not induce any acute toxicity after affected, especially the kidneys ingestion in humans. Toxins are found in all parts of the fungus, even in spores and mycelium. 30 grams - lethal dose for a child According to medical statistics, they cause up to 90- 95% of all fatal cases of mushroom poisoning.  Poisonous Fungi: Аmanita phalloides Symptoms do not begin until 6-24 hours after consumption. Symptoms:  Sever abdominal pains, vomiting, diarrhea, which persist for about 6-9 hours  “Honeymoon phase” where victim feels better for about 24 hours. During symptomless period internal organs, especially liver is acted upon by toxins.  Followed by gastrointestinal bleeding coma, and kidney failure. Death usually occur in 7 days.  If victim survives will require regular dialysis or Glomerulus of the kidney kidney transplant. after amatoxin poisoning  Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens.  Poisonous Fungi: Аmanita spp. Group 2 - Neurotoxic mushroom poisoning Muscarines Ibotenic acid/muscimol A. muscaria A. pantherina  Poisonous Fungi: Psilocybe Group 2 - Neurotoxic mushroom poisoning Psilocybin, Psilocin Stropharia squamosa Stropharia aeruginosa Psilocybe mexicana