Human Mycotoxicoses Research Articles

Mycotoxin Production in Fusarium According to Contemporary Species Concepts.

Fusarium is one of the most important genera of plant-pathogenic fungi in the world and arguably the world's most important mycotoxin-producing genus. Fusarium species produce a staggering array of toxic metabolites that contribute to plant disease and mycotoxicoses in humans and other animals. A thorough understanding of the mycotoxin potential of individual species is crucial for assessing the toxicological risks associated with Fusarium diseases. There are thousands of reports of mycotoxin production by various species, and there have been numerous attempts to summarize them. These efforts have been complicated by competing classification systems based on morphology, sexual compatibility, and phylogenetic relationships. The current depth of knowledge of Fusarium genomes and mycotoxin biosynthetic pathways provides insights into how mycotoxin production is distributedamong species and multispecies lineages (species complexes) in the genus as well as opportunities to clarify and predict mycotoxin risks connected with known and newly described species. Here, we summarize mycotoxin production in the genus Fusarium and how mycotoxin risk aligns with current phylogenetic species concepts.

The efficacy and effect on gut microbiota of an aflatoxin binder and a fumonisin esterase using an in vitro simulator of the human intestinal microbial ecosystem (SHIME®)

Mycotoxin intoxication is in general an acknowledged and tackled issue in animals. However, in several parts of the world, mycotoxicoses in humans still remain a relevant issue. The efficacy of two mycotoxin detoxifying animal feed additives, an aflatoxin bentonite clay binder and a fumonisin esterase, was investigated in a human child gut model, i.e. the in vitro Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). Additionally, the effect of the detoxifiers on gut microbiota was examined in the SHIME. After an initial two weeks of system stabilisation, aflatoxin B1 (AFB1) and fumonisin B1 (FB1) were added to the SHIME diet during one week. Next, the two detoxifiers and mycotoxins were added to the system for an additional week. The AFB1, FB1, hydrolysed FB1 (HFB1), partially hydrolysed FB1a and FB1b concentrations were determined in SHIME samples using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. The short-chain fatty acid (SCFA) concentrations were determined by a validated gas chromatography–mass spectrometry method. Colonic bacterial communities were analysed using metabarcoding, targeting the hypervariable V1-V3 regions of the 16S rRNA genes. The AFB1 and FB1 concentrations significantly decreased after the addition of the detoxifiers. Likewise, the concentration of HFB1 significantly increased. Concentrations of SCFAs remained generally stable throughout the experiment. No major changes in bacterial composition occurred during the experiment. The results demonstrate the promising effect of these detoxifiers in reducing AFB1 and FB1 concentrations in the human intestinal environment, without compromising the gastrointestinal microbiota.

Mycotoxins in Asia: is China in danger?

Mycotoxins such as aflatoxins, ochratoxins, fumonisins, deoxynivalenol and zearalenone are considered to be of particular concern in relation to human and animal health. Contamination of agricultural products by mycotoxins has become an important issue worldwide over the last three decades. Asia contributes a very large part of the globe with most developing countries in the tropical and subtropical regions favouring the growth of fungal species. There is a high potential of mycotoxin occurrence and a number of important mycotoxin outbreaks in Asia. In recent years, increasing number of survey in Asia with regard to prevalence of mycotoxins has evidenced the seriousness of mycotoxins problem in this continent. Among Asian countries, China is the most populous nation with a population of over 1.3 billion. Due to extensive and complex topography, diverse climate zones in China have provided various optimal environments for the growth of mycotoxins-producing fungi. It is evident that people in China have been exposed to various mycotoxins simultaneously in a frequent and chronic manner. Effort on investigation and monitoring with regard to mycotoxins contamination and exposure is necessitated for the sake of public health in this populous country. This review presents several mycotoxins exhibiting strong ecological link with human food supply in Asia. Human mycotoxicoses relating to these mycotoxins, especially in Asia, are highlighted and their contaminations of human foodstuffs in the 21st century in Asian countries are summarized. In particular, the current situation and control measures with regard to mycotoxin contamination in China are discussed.

ELP3 is involved in sexual and asexual development, virulence, and the oxidative stress response in Fusarium graminearum.

Fusarium graminearum is an important fungal plant pathogen that causes serious losses in cereal crop yields and mycotoxicoses in humans and livestock. In this study, we characterized an insertion mutant, Z39R9282, with pleiotropic defects in sexual development and virulence. We determined that the insertion occurred in a gene encoding an ortholog of yeast elongator complex protein 3 (ELP3). Deletion of elp3 led to significant defects in sexual and asexual development in F. graminearum. In the elp3 deletion mutant, the number of perithecia formed was reduced and maturation of perithecia was delayed. This mutant also produced morphologically abnormal ascospores and conidia. Histone acetylation in the elp3 deletion mutant was reduced compared with the wild type, which likely caused the developmental defects. Trichothecenes were not produced at detectable levels, and expression of trichothecene biosynthesis genes were significantly reduced in the elp3 deletion mutant. Infection of wheat heads revealed that the elp3 deletion mutant was unable to spread from inoculated florets to neighboring spikelets. Furthermore, the elp3 deletion mutant was more sensitive to oxidative stress than the wild type, and the expression of putative catalase genes was reduced. We demonstrate that elp3 functions in sexual and asexual development, virulence, and the oxidative stress response of F. graminearum by regulating the expression of genes involved in these various developmental processes.

The Impact Of Mycotoxicoses On Human History / Utjecaj Mikotoksikoza Na Povijest

AbstractMycotoxicoses are acute or chronic diseases of humans and animals caused by mycotoxins, toxic compounds produced by moulds. Of about 400 known mycotoxins only a small number are known to cause mycotoxicoses in humans. Organs that are most targeted are those in which mycotoxins are metabolised, that is, the liver and kidneys, but the lesions may affect the neurological, respiratory, digestive, haematological, endocrine, and immune systems as well.The epidemics of mycotoxicoses are often connected with times of famine, when population consumes food that would not be consumed in normal circumstances. Mycotoxicoses have influenced human history, causing demographic changes, migrations, or even influencing the outcomes of wars. Fortunately, epidemics affecting so many persons and with so many fatalities belong to the past. Today they only appear in small communities such as schools and factory canteens. This paper presents epidemics and pandemics of mycotoxicoses that influenced human history.

Occurrence of fumonisins and deoxynivalenol in stored maize used in industrial productions in Zaria Nigeria

Fifty three samples of four varieties of maize were obtained from 18 storage facilities in Zaria and its environs, all within Kaduna State, Nigeria and plated directly on potato dextrose agar (PDA). Samples which yielded Fusarium species were further tested for the presence of toxins. Seven samples yielded fumonisins alone, while both fumonisins and deoxynivalenol (DON) were found in three samples corresponding to 18.87% toxin contamination rate. Fusarium verticilloides was found to be the most toxigenic species occurring in eight toxin-contaminated samples while Fusarium proliferatum occurred only once. Three samples had fumonisin content above the 5 ppm threshold value while the other samples did not exceed the 1 ppm upper limit for DON. Fusarium contamination of grains used in industrial productions exists and thus there is the need for regulations guiding the storage and industrial utilisation of maize to minimize the risk of mycotoxicoses in humans and animals. Key words: Fumonisins, deoxynivalenol, stored maize, Fusarium, Zaria, mycotoxin, contamination, industrial productions

T-2 Toxin: Incidence and Toxicity in Poultry

T-2 toxin is the most toxic type A trichothecene mycotoxin. It is the secondary metabolite of the Fusarium fungi, and is common in grain and animal feed. Toxic effects have been shown both in experimental animals and in livestock. It has been implicated in several outbreaks of human mycotoxicoses. Toxic effects in poultry include inhibition of protein, DNA, and RNA synthesis, cytotoxicity, immunomodulation, cell lesions in the digestive tract, organs and skin, neural disturbances and low performance in poultry production (decreased weight gain, egg production, and hatchability). Concentrations of T-2 toxin in feed are usually low, and its immunosuppressive effects and secondary infections often make diagnosis difficult. If at the onset of the disease, a change in diet leads to health and performance improvements in animals, this may point to mycotoxin poisoning. Regular control of grain and feed samples is a valuable preventive measure, and it is accurate only if representative samples are tested. This article reviews the incidence and toxic effects of T-2 toxin in poultry.

Cytotoxicity of Fusarium mycotoxins to mammalian cell cultures as determined by the MTT bioassay

Fusarium mycotoxins occur worldwide in cereal grains and animal feeds and cause outbreaks of Fusarium mycotoxicoses in humans and animals. In this study mammalian cell cultures were used to screen the cytotoxicity of the most common Fusarium mycotoxins; deoxynivalenol (DON), zearalenone (ZEN), fumonisin B 1 (FB 1) and moniliformin (MON). The most sensitive cell line for each Fusarium mycotoxin was determined for further toxicological investigations as an alternative to whole animal testing. Chinese hamster ovary cells (CHO-K1) were found to be the most sensitive for DON and FB 1 with IC 50 values of 0.27 and 85.5 μg/ml, respectively, after 48-h exposure. The hepatocellular carcinoma cells (HepG2) showed the highest sensitivity to MON with IC 50 values of 39.5 for 48 h and 26.8 μg/ml for 72-h exposure. Balb/c mice keratinocyte cell line (C5-O) was found to be the most sensitive to ZEN with IC 50 of 24.1 μg/ml after 72-h exposure. DON was found the most cytotoxic to the cell cultures of all the mycotoxins tested, followed by MON, ZEN, and FB 1. The results indicated that CHO-K1, C5-O, and HepG2 cells were found to be the sensitive cell lines for preliminary screening of DON, ZEN and MON contaminated feed and food extracts, respectively.

Expression profile analysis of wild-type and fcc1 mutant strains of Fusarium verticillioides during fumonisin biosynthesis

Fusarium verticillioides produces a group of mycotoxins known as fumonisins that are associated with a variety of mycotoxicoses in humans and animals. In this study, DNA microarrays were constructed with expressed sequence tags (ESTs) from F. verticillioides. To identify genes with patterns of expression similar to the fumonisin biosynthetic ( FUM) genes, the microarray was probed with labeled cDNAs originating from a wild-type strain and a fcc1 mutant grown on maize and in a defined medium adjusted to either pH 3 or pH 8. The comparative analyses revealed differential expression of genes corresponding to 116 ESTs when the fungal strains were grown on maize. Under different pH conditions, 166 ESTs were differentially expressed, and 19 ESTs were identified that displayed expression patterns similar to the FUM ESTs. These results provide candidate genes with potential roles in fumonisin biosynthesis.

Risk from inhaled mycotoxins in indoor office and residential environments.

Mycotoxins are known to produce veterinary and human diseases when consumed with contaminated foods. Mycotoxins have also been proposed to cause adverse human health effects after inhalation exposure to mold in indoor residential, school, and office environments. Epidemiologic evidence has been inadequate to establish a causal relationship between indoor mold and nonallergic, toxigenic health effects. In this article, the authors model a maximum possible dose of mycotoxins that could be inhaled in 24 h of continuous exposure to a high concentration of mold spores containing the maximum reported concentration of aflatoxins B1 and B2, satratoxins G and H, fumitremorgens B and C, verruculogen, and trichoverrols A and B. These calculated doses are compared to effects data for the same mycotoxins. None of the maximum doses modeled were sufficiently high to cause any adverse effect. The model illustrates the inefficiency of delivery of mycotoxins via inhalation of mold spores, and suggests that the lack of association between mold exposure and mycotoxicoses in indoor environments is due to a requirement for extremely high airborne spore levels and extended periods of exposure to elicit a response. This model is further evidence that human mycotoxicoses are implausible following inhalation exposure to mycotoxins in mold-contaminated home, school, or office environments.

Comparison of Fumonisin B1 Biosynthesis in Maize Germ and Degermed Kernels by Fusarium verticillioides

Fusarium verticillioides produces a group of mycotoxins known as fumonisins in maize kernels. Fumonisins are associated with a variety of mycotoxicoses in humans and animals; thus, their presence in food is a considerable safety issue. This study addressed fumonisin B1 (FB1) production in two components of the maize kernel, namely the germ tissues and the degermed kernel. Growth of F. verticillioides was similar in colonized germ tissue and degermed kernels, but FB1 production was at least five times higher in degermed maize kernels than in germ tissue. Expression of the fumonisin polyketide synthase gene, FUM1, as measured by β-glucuronidase (GUS) and Northern blot analysis, followed the same pattern as FB1 production. Also correlated to FB1 was a concomitant drop in pH of the colonized degermed kernels. A time course experiment showed that degermed kernels inoculated with F. verticillioides became acidified over time (from pH 6.4 to 4.7 after 10 days of incubation), whereas colonized germ tissue became alkaline over the same period (from pH 6.5 to 8.5). Because conditions of acidic pH are conducive to FB1 production and alkaline pH is repressive, the observed correlation between the acidification of degermed kernels and the increase in FB1 provides one explanation for the observed differences in FB1 levels.

Toxins of filamentous fungi.

Mycotoxins are low-molecular-weight secondary metabolites of fungi. The most significant mycotoxins are contaminants of agricultural commodities, foods and feeds. Fungi that produce these toxins do so both prior to harvest and during storage. Although contamination of commodities by toxigenic fungi occurs frequently in areas with a hot and humid climate (i.e. conditions favorable for fungal growth), they can also be found in temperate conditions. Production of mycotoxins is dependent upon the type of producing fungus and environmental conditions such as the substrate, water activity (moisture and relative humidity), duration of exposure to stress conditions and microbial, insect or other animal interactions. Although outbreaks of mycotoxicoses in humans have been documented, several of these have not been well characterized, neither has a direct correlation between the mycotoxin and resulting toxic effect been well established in vivo. Even though the specific modes of action of most of the toxins are not well established, acute and chronic effects in prokaryotic and eukaryotic systems, including humans have been reported. The toxicity of the mycotoxins varies considerably with the toxin, the animal species exposed to it, and the extent of exposure, age and nutritional status. Most of the toxic effects of mycotoxins are limited to specific organs, but several mycotoxins affect many organs. Induction of cancer by some mycotoxins is a major concern as a chronic effect of these toxins. It is nearly impossible to eliminate mycotoxins from the foods and feed in spite of the regulatory efforts at the national and international levels to remove the contaminated commodities. This is because mycotoxins are highly stable compounds, the producing fungi are ubiquitous, and food contamination can occur both before and after harvest. Nevertheless, good farm management practices and adequate storage facilities minimize the toxin contamination problems. Current research is designed to develop natural biocontrol competitive fungi and to enhance host resistance against fungal growth or toxin production. These efforts could prevent toxin formation entirely. Rigorous programs for reducing the risk of human and animal exposure to contaminated foods and feed also include economically feasible and safe detoxification processes and dietary modifications. Although risk assessment has been made for some mycotoxins, additional, systematic epidemological data for human exposure is needed for establishing toxicological parameters for mycotoxins and the safe dose for humans. It is unreasonable to expect complete elimination of the mycotoxin problem. But multiple approaches will be needed to minimize the economic impact of the toxins on the entire agriculture industry and their harmfulness to human and animal health.

Mycotoxins as Causal Factors of Diseases in Humans

The criteria of human mycotoxicoses are discussed and the role of certain mycotoxins in human diseases highlighted, e.g. ergotoxins (ergotism), trichothecenes, T2-toxin (alimentary toxic aleukia), aflatoxins (primary liver cancer), ochratoxins (Balkan Endemic Nephropathy and chronic interstitial nephropathy) and fumonisins (oesophogeal cancer). The chemical properties and biochemical mechanism of action of aflatoxin B1 ochratoxin A and fumonisin B1 are discussed.

Mycotoxins, general view, chemistry and structure

Mycotoxins induce diverse and powerful biological effects in test systems; some are carcinogenic, mutagenic, teratogenic, estrogenic, hemorrhagic, immunotoxic, nephrotoxic, hepatotoxic, dermotoxic, and neurotoxic. Mycotoxins have been unambiguously linked to the etiology of several diseases in animals. The discovery of aflatoxins in the early 1960s led to the resurgence of interest in human mycotoxicoses; mycotoxins are now recognized as causal factors of primary liver cancer, ergotism and alimentary toxic aleukia. The fumonisins and ochratoxins are suspected of playing a role in the etiology of esophageal cancer and Balkan endemic nephrotoxicity, respectively.