Mycotoxins: the reign of terror

What is a mycotoxin?

Mycotoxins (a combination of the Greek word for « fungus » and the Latin word toxicum, meaning poison) are low molecular weight molecules produced as secondary metabolites by filamentous fungi that can be found as natural contaminants. These toxins have been shown to have adverse effects on both human and animal health, and are the cause of significant economic losses worldwide.

 

Mycotoxin intoxications are known since centuries in Europe and outbreaks occurred in irregular intervals. The historically most relevant outbreaks are related to Claviceps purpurea resulting in ergotism, “cardiac beriberi” in Asia, which is caused by consumption of Penicillum citreonigrum infested rice and the “alimentary toxic aleukia” in Russia caused by fusarium toxins in cereals. In 1960, more than 100.000 turkeys died in the United Kingdom, after being fed with aflatoxin contaminated peanut meal. This incidence, which was the beginning of the awareness for mycotoxins at global scale, is also known as the turkey “X” disease.

 

Nowadays, approximately 400 compounds are recognized as mycotoxins, although only about 30 molecules are considered as a threat to human and animal health. Additionally, the presence of toxin precursors, metabolites, degradation products, or the so-called masked mycotoxins is also a potential threat to consumer safety. Depending on their respective family, their range of actions includes cytotoxic, nephrotoxic, hepatotoxic, teratogenic, mutagenic, carcinogenic, immunosuppressive, and estrogenic effects.

 

The molecular weight of the mycotoxins ranges from 100 g/mol, such as moniliformin or nitropropionic acid to about 700 g/mol such as fumonisin B1 or beauvericin.  Mycotoxins can be found in fruit, milk, spices, wine, baby food, raw and processed cereals, eggs, meat… and since temperature and humidity are important parameters for the growth of fungi, climate change is anticipated to dramatically impact worldwide presence of mycotoxins.

Mycotoxins categories and classes

 

Mycotoxins are segmented into :

 

ü Aflatoxins : aflatoxin B1 is carcinogenic to humans and hepatotoxic.

ü Fusarium toxins, including subcategories :

 

o   Zearalenone (ZON) and its metabolites is not targeting a specific organ but systemic to humans and animals as they are endocrine disruptors.

o  Trichothecenes like DON and T-2 toxin interfere with protein synthesis and consequently result in numerous effects ranging from immune dysfunction to vomiting, which brought DON also the synonym “vomitoxin”.

o      Fumonisins show different carcinogenic and pathologic effects depending on the animal species affected,

 

ü Ergot alkaloids,

ü Patulin,

ü Ochratoxins,

ü Sterigmatocystins,

ü Citrinin,

ü Cyclopiazonic acids.

Mycotoxin Testing Market

 

Depending on the source, the global Mycotoxin Testing Market is expected to rise from its initial estimated value of USD 900 million in 2019, to 2.38 $billion by 2024. Classical analytical techniques for mycotoxins used are:

 

ü Methods based solely on UV absorbance,

ü Thin-Layer Chromatography (TLC),

ü Liquid chromatography (LC) coupled to mass-spectroscopy (MS),

ü Parallel to chromatographic methods, the development of :

 

o   antibodies specific to small molecules,

o   as well as molecular imprinted polymers (MIPS),

o   and aptamers.

 

 

In particular cost-efficient quick lateral flow devices are widely applied for multiplexed mycotoxin screening, while sensor based applications are described either as prototypes or as instruments for end-users. Antibodies are also used for preparative and cleaning immuno-affinity column step before HPLC, UPLC or MS/MS analysis but also as epitope mimics for competitive ELISA. The first polyclonal antibodies against mycotoxins were described more than 40 years ago, and followed by monoclonals in 1983.

Method

Advantages

Disadvantages

UV absorbance

Easy to handle

Disfavored since the desired selectivity of the signal is highly questionable

TLC

Technically easy to control. Fluorescence detection is still one of the most reliable and easy to implement methodologies.

Lack of automation

GC

High resolution, fast analysis

Limited to volatile samples

HPLC

High resolution, low limit of detection

Expensive. Operated in laboratory only.

MS/MS

High sensitivity

Matrix effects. Expensive. Skilled operators are needed. Time-consuming.

Lateral Flow

Low cost and practical. Rapid.

Cross-reactivity with masked mycotoxins. Enzyme stability. Limit of detection.

Biosensor

Rapid, sensitive

Generation of the receptor surface

 

Monoclonal antibodies against mycotoxins

 

Thanks to its unique ability and innovative technologies to break immune tolerance against small molecules, SYnAbs has generated monoclonal antibodies in mouse and rats species.