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Mycotoxin presentation final

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Mycotoxins
Introduction
Relatively low number of medically
important fungi for humans, when
compared to plant and insect pathogens
Mycotoxins: low-molecular weight natural
products produced as secondary
metabolites by filamentous fungi

Grouped depending on their disease causing
ability in vertebrates
Mycotoxicoses:
Diseases produced by the exposure to toxic fungal
metabolites
Dietary, Respiratory, Dermal……
Definitions & Generalities
Mycotoxin Gold Rush 1960-1975
Many scientists joined the well-funded
search for toxigenic agents produced by
fungi
300-400 compounds now recognized as
mycotoxins; 12+ groups
“Poisoning by natural means”
Similar to exposure to pesticides or heavy
metal residues
Usually accidental exposure
Mycotoxicoses…
Severity of the poison depends on:
Vitamin deficiency
Caloric deprivation
Alcohol abuse
Infectious disease status
Symptoms of disease depend on:
Type of mycotoxin
Amount and duration of exposure
Age, health and sex of exposed individual
Poorly understood factors:



Genetics
Dietary status
Interactions with other toxic substances
Mycotoxicoses…
The biggest problems with
mycotoxicoses



Heighten vulnerability to microbial
diseases
Worsen the effects of malnutrition
Interact synergistically with other toxins.
Definitions & Generalities
All mycotoxins are of fungal origin (microfungi)
BUT, not all toxic compounds produced by
fungi are called mycotoxins…
Examples:
Mycotoxins versus vertebrates and other animals
Mycotoxins - LOW conc. vs Ethanol - HIGH conc.
Antibiotics versus Bacteria
Phytotoxins versus Plants
Mushroom Poisons – macroscopic fungi, ingestion
because of misidentification
Who is at risk to being exposed to
mycotoxins?
Places of the world…
with poor methods of food handling and storage
where malnutrition is a problem
where few regulations exist to protect exposed
populations
In the US (and other developed countries) ?
Hispanic populations – consume more corn
products than the rest of the population
Inner city populations – more likely to live in
buildings harbor high levels of molds
Control of Mycotoxins
Good agricultural practice
Sufficient drying of crops after harvest
before storage
Prevent pre-harvest contamination by
increasing/developing host resistance by:



Plant breeding
Genetic engineering – enhance antifungal genes
Use of biocontrol agents that target regulatory genes in
the mycotoxin development
Improved government screening and
regulation programs
Major Mycotoxins Alphabetical listing—NOT potency
1.
2.
3.
4.
5.
6.
7.
8.
9.
Aflatoxins*
Citrinin
Ergot Alkaloids*
Fumonisins*
Ochratoxins
Patulin
Trichothecenes*
Zearalenone
Etc…
Aflatoxin
Isolated after Turkey X Disease
Consumption of a mold-contaminated peanut meal
Four major aflatoxins
B1, B2, G1 and G2
B1 is the most potent natural carcinogen
known, unfortunately major aflatoxin
produced by toxigenic strains
Major producers:
Aspergillus flavus and Aspergillus parasiticus
Aflatoxin
Natural contamination of agricultural products:
Cereals, figs, oilseeds, nuts, tobacco, etc.
Contaminated in field before harvest
More problems during storage – moist & humidity
Contamination of grain causes:
Increased mortality in farm animals
Lowers the value of exported grain as animal feeds
Location of biggest problem is countries where
the population is facing starvation or regulations
non-existent or not enforced
Aflatoxin
Mechanism of action:

Cytochrome enzymes convert to an epoxide
that binds to N7 of guanine
Eventual mutation of G/C to A/T
Extrapolate test animal results to human

Difficult because different enzymes
Human carcinogen– liver cancer


China, Philippines, Thailand, and many African
countries
Risk factor: Hepatitis B
Ergot Alkaloids
Produced by Claviceps, primarily
a grass pathogen
Associated with disease since 600 BCE
Common in Europe during Middle Ages



“..noxious pustule in the ear of grain”
Eating cereals infected with a toxic cocktail of
alkaloids with ergoline ring systems
St Anthony’s Fire – bread from contaminated
flour
Gangrenous – blood supply to the extremities
Convulsive – affect CNS
Ergot Alkaloids
Currently a veterinary problem


Cattle, sheep, pigs, chicken
Symptoms
Gangrene, abortions, convulsions, suppression of
lactation, hypersensitivity
Mechanism of action:


Induce smooth muscle contraction
Midwives administer to women in labour as a
natural product to accelerate uterine
contractions
Ergot Alkaloids - History
1943 – Birth of LSD





Hoffman - research involved varying the
amino alcohol of lysergic acid
Developed Methergine – control hemorrhaging
after childbirth
Continued research…
Accidentally ingested compound #25 and
discovered the hallucigenic properties of
lysergic acid diethylamide (LSD)
Marketed as Delysid – unsuccessful treatment
of schizophrenia
Ergot Alkaloids - Uses
MK-ULTRA code name

After WWII - CIA used as a truth serum for
interrogating suspected communists
Hypothesized Salem witchcraft affair probably
the result of convulsive ergotism related to
consumption of rye with Claviceps ergot
alkaloids cocktail
Ergotamine – used to treat migraine headaches
Ergot derivatives – used in the treatment of
Parkinsonism
Fumonisin
Produced by:


Fusarium spp.
Alternaria alternata
Economical importance:

Fusarium verticillioides
A corn endophyte in vegetative and reproductive
tissue; usually plant is asymptomatic

Cause seedling blight, stalk and ear rot
ALL corn has resident fungus, most strains
do not produce the toxic compound
Fuminosin
Medical Importance:



Interferes with sphingolipid metabolism in
animals and vertebrates
Cause leukoencephalomalacia (hole in head
syndrome) in birds and rabbits
Humans:
Can cause neural tube defects
Linked to esophageal cancer



Charleston, SC – 7 samples
Isolated high concentration in corn meal and corn grits
US city with highest incidence of esophageal cancer
among African-Americans
Trichothecenes
Nonmacrocyclic
Macrocyclic
Type A Group
Type B Group
AKA Vomitoxin
Trichothecenes
Over 60 compounds produced by:



Fusarium, Phomopsis, Trichoderma, Myrothecium,
Stachybotrys, Trichothecium…
Common food & feed contaminants
Consumption:
Alimentary hemorrhaging and vomiting

Skin contact:
Dermatitis
Collective problem:

Extreme potent inhibitors of eukaryotic protein
synthesis, specifically peptidyl transferase
Eating mold grain
Trichothecenes, Deoxynivalenol
Most common mycotoxin found in
grain

Especially barley
A.k.a. Vomitoxin or food refusal factor

Farm animal – nausea, vomit, diarrhea,
weight loss and food refusal
Trichothecenes, T-2 &
diacetoxyscirpenol
Cytotoxic activity
Immunosuppressive effect
Human disease:

Alimentary toxic aleukia
Inflammation of skin, vomiting,
necrosis of oral cavity, bleeding (nose,
mouth & vagina), and CNS problems
Trichothecenes, Stachybotrys
Wet building material harbor organism

Gypsum board, ceiling tiles, wood fiber board,
dust lined A/C vents
Mycotoxin people talk about when
referring to Sick-building Syndrome
Shown to cause pulmonary bleeding in
infants when exposed for prolonged times
Described as the 10th plague visited on
Egypt
Hurricane Katrina, New Orleans Stchybotyrs growing above flood line
Carpet Monsters Killer Spores
Interesting e-book in USF Library (Chap 8)
Author is N.Money who studies biophysics
Basidiospore discharge
Explains basics of immunology/allergies
Addresses indoor air quality/role of fungi
Addresses mycotoxin of Stachybotrys in
neonatal hospital unit
Additional Reading:
POISONS of the PastMolds, Epidemics and
History

By Mary Kilbourne Matossian
References
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