**5. Mycotoxins and mycotoxin-producing conditions**

*Fusarium* mycotoxins are very common worldwide. They exist in many plants and in various compositions. The major *Fusarium* mycotoxins are FB1, trichothecenes [e.g. DON, nivalenol (NIV), T-2 and ZEN] [19–21]. The most important species that is common in Europe is *F. graminearum*. In the past, *Fusarium* genus members were mostly not considered as pathogens in the field. However, *F. proliferatum* and *F. verticillioides* are of great importance as the main producers of the most dangerous *Fusarium* mycotoxins [22, 23]. Worldwide mycotoxin occurrence in maize and wheat/bran samples with their median and maximum levels were given in **Figure 1** [24, 25].

Shi et al. [5] evaluated the mycotoxins from 20 of the most common *Fusarium* species and sorted them into the following three groups based on their molecular characterization (**Figure 2**). Group-1 comprised fusaric acid producers and was further divided into two subgroups. Subgroup-I comprised *F. fujikuroi*, *F. solani*, *F. verticillioides* and *F. proliferatum* that produce fusaric acid and fumonisins; subgroup-II comprised *F. musae*, *F. equiseti*, *F. temperatum*, *F. subglutinans*, *F. tricinctum*, *F. oxysporum*, *F. concentricum*, *F. sacchari* and *F. andiyazi* that produce only fusaric acid. According to the classification of *Fusarium* mycotoxins, type-A trichothecene producers comprising *F. polyphialidicum*, *F. sporotrichioides* and *F. langsethiae* formed the Group-II, and type-B trichothecene producers comprising *F. meridionale*, *F. culmorum*, *F. graminearum* and *F. poae* formed Group-III.

In the presence of *Fusarium* species in plants, the contamination with fumonisins was shown in wheat [26], garlic [27], and asparagus [28]. The most affected plants, that is, maize, beans, soybean [29], rice [30], and sorghum [31] were specifically infected by *Gibberella fujikuroi* species complex (*F. proliferatum, F. verticillioides* and *F. andiyazi*) [29, 32].

Guidance values for *Fusarium* mycotoxins were set in Commission Recommendation 2006/576/ EC [33]. Recommended values for the *Fusarium* mycotoxins DON, ZEA and fumonisins were set in "Commission Recommendation 2006/576/EC" [33]. For T-2 and HT-2 toxin, indicative

> levels for cereals and cereals products were set in "Commission Recommendation 2013/165/ EU" [34]. Maximum limits for DON, ZEA, fumonisins, T-2 and HT-2 toxins have been set for

> **Figure 2.** Mycotoxin classification according main four *Fusarium* species (A) *F. proliferatum* (B) *F*. *langsethiae* (C) *F. graminearum*

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Resistance of *Fusarium* to antifungal drugs has been defined by many researchers. It is known that many FSSC members cause fusarial onychomycosis [36]. *F. solani* showed more resistance to antifungal agents than others [37]. The effect of azole antifungals used clinically is depend on a particular site, lanosterol-14α-demethylase. While imidazole or triazole rings are important for conferring the therapeutic effect in animals, epoxiconazole, propiconazole, difenoconazole, bromuconazole and tebuconazole are used for plants. *Fusarium* spp. are resistant

Tupaki-Sreepurna et al. [39] reported that FSSC members, mainly *F. falciforme* and *F. keratoplasticum*, showed multi-drug resistance against caspofungin and azoles. Only a few antifungal agents (voriconazole, posaconazole and amphotericin B) showed *in-vitro* activity against

Conversely, the echinocandins are lipopeptide molecules which effectively work by inhibiting 1,3-β-D-glucan synthase of the fungal membrane. If a change occurs in the amino acid residues of β-1,3-glucan synthase enzyme subunits (FKS subunits) in the treatment process, it

cereals and by-products according to the production technology used [35].

**6. Fungal resistance**

and (D) in PDA, rice and maize medium [5].

*F. falciforme* and *F. keratoplasticum* [40].

may lead to increased drug resistance [41, 42].

to azoles [38].

**Figure 1.** Worldwide mycotoxin occurrence (μg/kg) in maize and wheat/bran samples (A, C: Median of positive samples; B, D: Maximum levels) [24, 25].

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**Figure 2.** Mycotoxin classification according main four *Fusarium* species (A) *F. proliferatum* (B) *F*. *langsethiae* (C) *F. graminearum* and (D) in PDA, rice and maize medium [5].

levels for cereals and cereals products were set in "Commission Recommendation 2013/165/ EU" [34]. Maximum limits for DON, ZEA, fumonisins, T-2 and HT-2 toxins have been set for cereals and by-products according to the production technology used [35].
