Trichothecene

They are produced by fungi of the genera Fusarium, Myrothecium, Trichoderma, Podostroma, Trichothecium, Cephalosporium, Verticimonosporium [ceb; nl; sv], Stachybotrys (most in Hypocreales) and possibly others.

All trichothecenes share the cyclic sesquiterpene structure but differ in the type of functional group attached to the carbon backbone.

[4] They are produced on many different grains such as wheat, oats, or maize by various Fusarium species including F. graminearum, F. sporotrichioides, F. poae, and F. equiseti.

[9] These two functional groups are primarily responsible for trichothecenes' ability to inhibit protein synthesis and incur general cytotoxic effects.

[9] These functional groups govern the properties of an individual trichothecene and also serve as the basis for the most commonly used classification system for this family of toxins.

Additionally, J. F. Grove proposed a classification of trichothecenes into three groups that was also based upon the functional substitution patterns of the ring skeleton.

[15] Inhibition at elongation most likely occurs due to trichothecenes preventing the function of peptidyl transferase, the enzyme which catalyzes the formation of new peptide bonds on the 60s ribosomal subunit.

[15] Trichothecenes also can affect general cellular enzyme function as the 12,13-epoxy moiety is susceptible to nucleophilic attack by active-site thiol groups.

Activated c-jun acts as a transcription factor in the cell nucleus for proteins important for facilitating the downstream apoptotic pathway.

[21] The specific toxicity varies depending on the particular toxin and animal species, however the route of administration plays a significantly higher role in determining lethality.

The small amphipathic nature of trichothecenes allows them to easily cross cell membranes[11] and interact with different organelles such as the mitochondria,[30][31] endoplasmic reticulum (ER).

The response in the body to the mycotoxin, alimentary toxic aleukia, occurs several days after consumption, in four stages: Infection can be triggered by an injury as minor as a cut, scratch, or abrasion.

Around 100,000 people (60% mortality rate) began to suffer and die from alimentary toxic aleukia, a lethal disease with symptoms resembling radiation poisoning.

[40] Trichothecenes make an ideal biological warfare agent, being lethal and inexpensive to produce in large quantities, stable as an aerosol for dispersion, and without effective vaccination/treatment.

These mycotoxins account for millions of dollars annually in losses, due to factors that are often beyond human control (environmental, ecological, or storage method).

The fungal propagation and production is enhanced in tropical conditions with high temperatures and moisture levels; monsoons, flash floods and unseasoned rains during harvest.

Severity of symptoms depends on the dose and type of exposure, but treatment is primarily focused on supporting bodily systems damaged by the mycotoxin.

[68] Development of severe cardiopulmonary distress may require intubation and additional drug treatments to stabilize heart and lung activity.

[69] Here, the charcoal acts as a porous substance for the toxin to bind, preventing its absorption through the gastrointestinal tract and increasing its removal from the body through bowel excretion.

Generally, a good diet rich in probiotics, vitamins and nutrients, proteins, and lipids is thought to be effective in reducing the symptoms of trichothecene poisoning.

[70] Incubation with aqueous ozone at approximately 25 ppm has also been shown to degrade a variety of trichothecenes through a mechanism involving oxidation of the 9, 10 carbon double bond.

Many microbes, including bacteria, yeast, and fungi, have evolved enzymatic gene products which facilitate the specific and efficient degradation of trichothecene mycotoxins.

For example, the Eubacteria strain BBSH 797 produces de-epoxidase enzymes which reduce the 12,13 carbon epoxide ring to a double bond group.

This meant they would be inneffective or quick to remediate in open attacks or water supply poisoning, where it might be exposed to sunlight, boiled, or conditioned with chlorine.

Chemical structure of trichothecenes
The core structure of all major trichothecenes with major examples from each classification type. Identifying functional groups for the classification type are highlighted in red.
Trichothecenes accelerates reactive oxygen species production in cells, which in turn mediates the induction of the programmed cell death pathway in cells
Alimentary toxic aleukia response stages
Biological approach to trichothecene decontamination. De-epoxidases are capable of reducing epoxide rings (red) to double bond groups (green) which significantly reduces the toxicity of trichothecenes.