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BACKGROUND: Fresh ginseng is typically accompanied by soil after harvest, leading to contamination with harmful fungi during storage and distribution. In this study, we investigated the incidence of fungal contamination in fresh ginseng (5–6 years old) purchased from 22 different stores in Geumsan, Korea. RESULTS: The incidence of fungal contamination in the samples was 67.4–111.5%. Fusarium solani was the most abundant species in the head (38.5%) and fine root (19.3%) parts of the ginseng samples, whereas F. oxysporum was the most abundant in the main root (22.0%) part. We isolated Aspergillus, Fusarium and Penicillium spp. (total number of isolates: 395) from the ginseng samples, and 138 isolates were identified using phylogenetic analysis. Polymerase chain reaction‐based screening of 65 mycotoxin‐producing species revealed that two P. expansum isolates were positive for citrinin and/or patulin, and five F. oxysporum isolates were positive for fumonisin biosynthesis gene. One P. expansum isolate produced 738.0 mg kg−1 patulin, and the other produced 10.4 mg kg−1 citrinin and 12.0 mg kg−1 patulin on potato dextrose agar (PDA) medium. Among the 47 representative F. oxysporum isolates, 43 (91.5%) produced beauvericin (0.1–15.4 mg kg−1) and four of them (8.5%) produced enniatin B and enniatin B1 (0.1–1.8 mg kg−1) as well. However, none of these toxins was detected in fresh ginseng samples. CONCLUSION: Fusarium solani and F. oxysporum were the most abundant species in fresh ginseng samples. Most F. oxysporum (43) and P. expansum (2) strains isolated from fresh ginseng produced beauvericin and enniatins (B and B1), and patulin or citrinin, respectively, on PDA medium. This is the first report of the mycotoxigenic potential of P. expansum and F. oxysporum strains isolated from fresh ginseng. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The distribution of mycotoxins during cheese production and storage is a complex process that depends on several factors, including milk quality, cheese type, storage conditions, and the presence of competing microorganisms. This paper investigates the occurrence and distribution of mycotoxins in curd/cheese/whey during different cheese processes and the effect of ripening/storage time on mycotoxin levels in the final product using a review approach. The paper covers the major mycotoxins that can contaminate cheese, including aflatoxins, ochratoxin‐A, roquefortine‐C, mycophenolic acid, and beauvericin. Overall, it synthesises the existing understanding of the spread of mycotoxins during cheese production and storage. [ABSTRACT FROM AUTHOR]

Pineapple Fruitlet Core Rot (FCR) is a fungal disease characterized by a multi-pathogen pathosystem. Recently, Fusarium proliferatum, Fusarium oxysporum, and Talaromyces stollii joined the set of FCR pathogens until then exclusively attributed to Fusarium ananatum. The particularity of FCR relies on the presence of healthy and diseased fruitlets within the same infructescence. The mycobiomes associated with these two types of tissues suggested that disease occurrence might be triggered by or linked to an ecological chemical communication-promoting pathogen(s) development within the fungal community. Interactions between the four recently identified pathogens were deciphered by in vitro pairwise co-culture bioassays. Both fungal growth and mycotoxin production patterns were monitored for 10 days. Results evidenced that Talaromyces stollii was the main fungal antagonist of Fusarium species, reducing by 22% the growth of Fusarium proliferatum. A collapse of beauvericin content was observed when FCR pathogens were cross-challenged while fumonisin concentrations were increased by up to 7-fold. Antagonism between Fusarium species and Talaromyces stollii was supported by the diffusion of a red pigmentation and droplets of red exudate at the mycelium surface. This study revealed that secondary metabolites could shape the fungal pathogenic community of a pineapple fruitlet and contribute to virulence promoting FCR establishment. [ABSTRACT FROM AUTHOR]

Poultry farming has developed into one of Algeria's most productive industrial farming because of the growing demand for sources of protein among Algerian society. Laying hen feed consists mainly of cereals, which can be contaminated with molds and subsequently with their secondary metabolites known as mycotoxins. These later can pose a serious danger to the production and quality of eggs in the commercial layer industry. This work focuses on the detection of emerging mycotoxins, mainly enniatins (ENNs) and beauvericin (BEA), in poultry feed and eggs from different locations in Algeria. Two different QuEChERS-based extractions were established to extract ENNs and BEA from chicken feed and eggs. The determination of mycotoxin occurrence was achieved by a UHPLC-MS/MS method using 0.1% (v/v) formic acid in water and MeOH as mobile phase, an ESI interface operating in positive mode, and a triple quadrupole mass spectrometer operating in MRM for the detection. Matrix-matched calibration curves were carried out for both matrices, obtaining good linearity (R2 > 0.99). The method performance was assessed in terms of extraction recovery (from 87 to 107%), matrix effect (from − 47 to − 86%), precision (RSD < 15%), and limits of quantitation (≤ 1.1 µg/kg for feed and ≤ 0.8 µg/kg for eggs). The analysis of 10 chicken feed samples and 35 egg samples composed of a 10-egg pool each showed that ENN B1 was the most common mycotoxin (i.e., found in 9 feed samples) with contamination levels ranging from 3.6 to 41.5 µg/kg, while BEA was detected only in one feed sample (12 µg/kg). However, eggs were not found to be contaminated with any mycotoxin at the detection limit levels. Our findings indicate that the searched mycotoxins are present in traces in feed and absent in eggs. This can be explained by the application of a mycotoxin binder. However, this does not put a stop on the conduction of additional research and ultimately setting regulations to prevent the occurrence of emerging mycotoxins. [ABSTRACT FROM AUTHOR]

A total of 769 wheat kernels collected from six provinces in China were analyzed for beauvericin (BEA) and four enniatins (ENNs), namely, ENA, ENA1, ENB and ENB1, using a solid phase extraction (SPE) technique with ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The results show that the predominant toxin was BEA, which had a maximum of 387.67 μg/kg and an average of 37.69 μg/kg. With regard to ENNs, the prevalence and average concentrations of ENB and ENB1 were higher than those of ENA and ENA1. The geographical distribution of BEA and ENNs varied. Hubei and Shandong exhibited the highest and lowest positive rates of BEA and ENNs (13.46% and 87.5%, respectively). However, no significant difference was observed among these six provinces. There was a co-occurrence of BEA and ENNs, and 42.26% of samples were simultaneously detected with two or more toxins. Moreover, a significant linear correlation in concentrations was observed between the four ENN analogs (r range: 0.75~0.96, p < 0.05). This survey reveals that the contamination and co-contamination of BEA and ENNs in Chinese wheat kernels were very common. [ABSTRACT FROM AUTHOR]

Abstract Risk assessment (RA) of microbial secondary metabolites (SM) is part of the EU approval process for microbial active substances (AS) used in plant protection products (PPP). As the number of potentially produced microbial SM may be high for a certain microbial strain and existing information on the metabolites often are low, data gaps are frequently identified during the RA. Often, RA cannot conclusively clarify the toxicological relevance of the individual substances. This work presents data and RA conclusions on four metabolites, Beauvericin, 2,3-deepoxy-2,3-didehydro-rhizoxin (DDR), Leucinostatin A and Swainsonin in detail as examples for the challenging process of RA. To overcome the problem of incomplete assessment reports, RA of microbial AS for PPP is in need of new approaches. In view of the Next Generation Risk Assessment (NGRA), the combination of literature data, omic-methods, in vitro and in silico methods combined in adverse outcome pathways (AOPs) can be used for an efficient and targeted identification and assessment of metabolites of concern (MoC).

Risk assessment (RA) of microbial secondary metabolites (SM) is part of the EU approval process for microbial active substances (AS) used in plant protection products (PPP). As the number of potentially produced microbial SM may be high for a certain microbial strain and existing information on the metabolites often are low, data gaps are frequently identified during the RA. Often, RA cannot conclusively clarify the toxicological relevance of the individual substances. This work presents data and RA conclusions on four metabolites, Beauvericin, 2,3-deepoxy-2,3-didehydro-rhizoxin (DDR), Leucinostatin A and Swainsonin in detail as examples for the challenging process of RA. To overcome the problem of incomplete assessment reports, RA of microbial AS for PPP is in need of new approaches. In view of the Next Generation Risk Assessment (NGRA), the combination of literature data, omic-methods, in vitro and in silico methods combined in adverse outcome pathways (AOPs) can be used for an efficient and targeted identification and assessment of metabolites of concern (MoC). [ABSTRACT FROM AUTHOR]

Beauvericin is an emerging Fusariotoxin naturally occurring in cereal grains throughout the world whereas glyphosate (N-phosphonomethyl-glycine) is a non-selective systemic herbicide used worldwide. The purpose of this study is to evaluate a newly developed ovarian cell culture system (that includes both granulosa and theca cells) as an in vitro model for toxicological studies. Specifically, the effects of beauvericin and glyphosate in formulation with Roundup on ovarian cell numbers and steroid production were evaluated. Ovaries collected from cattle without luteal structures were sliced into 30–70 pieces each, and granulosa and theca cells were collected. Harvested cells were cultured for 48 h in 10% fetal bovine serum-containing medium followed by 48 h in serum-free medium containing testosterone (500 ng/mL; as an estrogen precursor) with the following eight treatments: (1) controls, (2) FSH (30 ng/mL) alone, (3) FSH plus insulin-like growth factor-1 (IGF1; 30 ng/mL), (4) FSH plus IGF1 plus beauvericin (3 µM), (5) FSH plus IGF1 plus glyphosate in Roundup (10 µg/mL), (6) FSH plus IGF1 plus fibroblast growth factor 9 (FGF9, 30 ng/mL), (7) a negative control without added testosterone, and (8) IGF1 plus LH (30 ng/mL) with basal medium without added testosterone. In the presence of FSH, IGF1 significantly increased cell numbers, estradiol and progesterone production by severalfold. Glyphosate in Roundup formulation significantly inhibited IGF1-induced cell numbers and estradiol and progesterone production by 89–94%. Beauvericin inhibited IGF1-induced cell numbers and estradiol and progesterone by 50–97% production. LH plus IGF1 significantly increased androstenedione secretion compared with controls without added testosterone indicating the presence of theca cells. In conclusion, the present study demonstrates that toxicological effects of beauvericin and glyphosate in Roundup formulation are observed in a newly developed ovarian cell model system and further confirms that both glyphosate and beauvericin may have the potential to impair reproductive function in cattle. [ABSTRACT FROM AUTHOR]

There is still considerable controversy about the relative risk of mycotoxin exposure associated with the consumption of organic and conventional cereals. Using validated protocols, we carried out a systematic literature review and meta-analyses of data on the incidence and concentrations of mycotoxins produced by Fusarium, Claviceps, Penicillium, and Aspergillus species in organic and conventional cereal grains/products. The standard weighted meta-analysis of concentration data detected a significant effect of production system (organic vs. conventional) only for the Fusarium mycotoxins deoxynivalenol, with concentrations ~50% higher in conventional than organic cereal grains/products (p < 0.0001). Weighted meta-analyses of incidence data and unweighted metaanalyses of concentration data also detected small, but significant effects of production system on the incidence and/or concentrations of T-2/HT-2 toxins, zearalenone, enniatin, beauvericin, ochratoxin A (OTA), and aflatoxins. Multilevel meta-analyses identified climatic conditions, cereal species, study type, and analytical methods used as important confounding factors for the effects of production system. Overall, results from this study suggest that (i) Fusarium mycotoxin contamination decreased between the 1990s and 2020, (ii) contamination levels are similar in organic and conventional cereals used for human consumption, and (iii) maintaining OTA concentrations below the maximum contamination levels (3.0 µg/kg) set by the EU remains a major challenge. [ABSTRACT FROM AUTHOR]

Drug discovery was initially attributed to coincidence or experimental research. Historically, the traditional approaches were complex, lengthy, and expensive, entailing costly random screening of synthesized compounds or natural products coupled with in vivo validation largely depending on the availability of appropriate animal models. Currently, in silico modeling has become a vital tool for drug discovery and repurposing. Molecular docking and dynamic simulations are being used to find the best match between a ligand and a molecule, an approach that could help predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana, being originally studied for its potential use as a pesticide. BEA is now considered a molecule of interest for its possible use in diverse biotechnological applications in the pharmaceutical industry and medicine. In this manuscript, we provide an overview of the repurposing of BEA as a potential therapeutic agent for multiple diseases. Furthermore, considerable emphasis is given to the fundamental role of in silico techniques to (i) further investigate the activity spectrum of BEA, a secondary metabolite, and (ii) elucidate its mode of action. [ABSTRACT FROM AUTHOR]

Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks.

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In this work, a complete study of the distribution of emerging mycotoxins in the human body has been carried out. Specifically, the presence of enniatins (A, A1, B, B1) and beauvericin has been monitored in brain, lung, kidney, fat, liver, and heart samples. A unique methodology based on solid–liquid extraction (SLE) followed by dispersive liquid–liquid microextraction (DLLME) was proposed for the six different matrices. Mycotoxin isolation was performed by adding ultrapure water, acetonitrile, and sodium chloride to the tissue sample for SLE, while the DLLME step was performed using chloroform as extraction solvent. Subsequently, the analysis was carried out by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC–MS/MS). The proposed method allowed limits of quantification (LOQs) to be obtained in a range of 0.001–0.150 ng g−1, depending on the tissue and mycotoxin. The precision was investigated intraday and interday, not exceeding of 9.8% of relative standard deviation. In addition, trueness studies achieved 75 to 115% at a mycotoxin concentration of 25 ng g−1 and from 82 to 118% at 5 ng g−1. The application of this methodology to 26 forensic autopsies demonstrated the bioaccumulation of emerging mycotoxins in the human body since all mycotoxins were detected in tissues. Enniatin B (ENNB) showed a high occurrence, being detected in 100% of liver (7 ± 13 ng g−1) and fat samples (0.2 ± 0.8 ng g−1). The lung had a high incidence of all emerging mycotoxins at low concentrations, while ENNB, ENNB1, and ENNA1 were not quantifiable in heart samples. Co-occurrence of mycotoxins was also investigated, and statistical tests were applied to evaluate the distribution of these mycotoxins in the human body. [ABSTRACT FROM AUTHOR]

Mycotoxins, produced by fungi, frequently occur at different stages in the food supply chain between pre- and postharvest. Globally produced cereal crops are known to be highly susceptible to contamination, thus constituting a major public health concern. Among the encountered mycotoxigenic fungi in cereals, Fusarium spp. are the most frequent and produce both regulated (i.e., T-2 toxin, deoxynivalenol -DON-, zearalenone -ZEA-) and emerging (i.e., enniatins -ENNs-, beauvericin -BEA-) mycotoxins. In this study, we investigated the in vitro cytotoxic effects of regulated and emerging fusariotoxins on HepaRG cells in 2D and 3D models using undifferentiated and differentiated cells. We also studied the impact of ENN B1 and ENN B exposure on gene expression of HepaRG spheroids. Gene expression profiling pinpointed the differentially expressed genes (DEGs) and overall similar pathways were involved in responses to mycotoxin exposure. Complement cascades, metabolism, steroid hormones, bile secretion, and cholesterol pathways were all negatively impacted by both ENNs. For cholesterol biosynthesis, 23/27 genes were significantly down-regulated and could be correlated to a 30% reduction in cholesterol levels. Our results show the impact of ENNs on the cholesterol biosynthesis pathway for the first time. This finding suggests a potential negative effect on human health due to the essential role this pathway plays. [ABSTRACT FROM AUTHOR]

In current study, Fusarium mycotoxin, beauvericin (BEA), has endocrine disrupting potential through suppressing the exogenous androgen receptor (AR)-mediated transcriptional activation. BEA was classified as an AR antagonist, with IC30 and IC50 values indicating that it suppressed AR dimerization in the cytosol. BEA suppress the translocation of cytosolic activated ARs to the nucleus via exogenous androgens. Furthermore, we investigated the impact of environmental conditions for BEA production on rice cereal using response surface methodology. The environmental factors affecting the production of BEA, namely temperature, initial moisture content, and growth time were optimized at 20.28 °C, 42.79 % (w/w), and 17.31 days, respectively. To the best of our knowledge, this is the first report showing that BEA has endocrine disrupting potential through suppressing translocation of cytosolic ARs to nucleus, and temperature, initial moisture content, and growth time are important influencing environmental factors for its biosynthesis in Fusarium strains on cereal.

Pineapple Fruitlet Core Rot (FCR) is a fungal disease characterized by a multi-pathogen pathosystem. Recently, Fusarium proliferatum, Fusarium oxysporum, and Talaromyces stollii joined the set of FCR pathogens until then exclusively attributed to Fusarium ananatum. The particularity of FCR relies on the presence of healthy and diseased fruitlets within the same infructescence. The mycobiomes associated with these two types of tissues suggested that disease occurrence might be triggered by or linked to an ecological chemical communication-promoting pathogen(s) development within the fungal community. Interactions between the four recently identified pathogens were deciphered by in vitro pairwise co-culture bioassays. Both fungal growth and mycotoxin production patterns were monitored for 10 days. Results evidenced that Talaromyces stollii was the main fungal antagonist of Fusarium species, reducing by 22% the growth of Fusarium proliferatum. A collapse of beauvericin content was observed when FCR pathogens were cross-challenged while fumonisin concentrations were increased by up to 7-fold. Antagonism between Fusarium species and Talaromyces stollii was supported by the diffusion of a red pigmentation and droplets of red exudate at the mycelium surface. This study revealed that secondary metabolites could shape the fungal pathogenic community of a pineapple fruitlet and contribute to virulence promoting FCR establishment.

Using phylogenetic analysis of three loci of Fusarium subglutinans sensu lato strains isolated from wheat and rape, the strains were re-identified as F. temperatum. This is the first report of this fungus in a cruciferous plant's mycobiota. Analysis of F. temperatum pathogenicity to rape revealed that the pathogen reduced the germination of seeds by 15%, and decreased seedling length by 13–18%. Fusarium temperatum strains did not produce fumonisins, but produced beauvericin and moniliformin. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA), a naturally occurring cyclic peptide with good pharmacological activity, has been widely explored in anticancer research. Although BEA is toxic, studies have demonstrated its antioxidant activity. However, to date, the antioxidant mechanisms of BEA remain unclear. Herein, we conducted a comprehensive and detailed study of the antioxidant mechanism of BEA using an untargeted metabolomics approach, subsequently validating the results. BEA concentrations of 0.5 and 1 μM significantly inhibited H2O2-induced oxidative stress (OS), decreased reactive oxygen species levels in PC-12 cells, and restored the mitochondrial membrane potential. Untargeted metabolomics indicated that BEA was primarily involved in lipid-related metabolism, suggesting its role in resisting OS in PC-12 cells by participating in lipid metabolism. BEA combated OS damage by increasing phosphatidylcholine, phosphatidylethanolamine, and sphingolipid levels. In the current study, BEA upregulated proteins related to the PI3K/AKT/mTOR pathway, thereby promoting cell survival. These findings support the antioxidant activity of BEA at low concentrations, warranting further research into its pharmacological effects.

Drug discovery was initially attributed to coincidence or experimental research. Historically, the traditional approaches were complex, lengthy, and expensive, entailing costly random screening of synthesized compounds or natural products coupled with in vivo validation largely depending on the availability of appropriate animal models. Currently, in silico modeling has become a vital tool for drug discovery and repurposing. Molecular docking and dynamic simulations are being used to find the best match between a ligand and a molecule, an approach that could help predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana, being originally studied for its potential use as a pesticide. BEA is now considered a molecule of interest for its possible use in diverse biotechnological applications in the pharmaceutical industry and medicine. In this manuscript, we provide an overview of the repurposing of BEA as a potential therapeutic agent for multiple diseases. Furthermore, considerable emphasis is given to the fundamental role of in silico techniques to (i) further investigate the activity spectrum of BEA, a secondary metabolite, and (ii) elucidate its mode of action.

The enniatins A, A1, B and B1 (ENNs) and beauvericin (BEA) are structurally related compounds produced by Fusarium species. They occur as contaminants in cereals, such as wheat, barley and maize. They are called “emerging mycotoxins”, because they have been reported in feed and food and their toxic effects are not fully known. Data on their levels in food (especially in milk) are limited. The study aimed to evaluate the occurrence of ENNs and BEA in milk.

The molecular structure of mycotoxins enniatin B and beauvericin, which are used as ionophores, was studied using density functional theory in various symmetry groups and singly charged states. We have shown that the charge addition or removal causes significant structural changes. Unlike the neutral C3 molecules, the stability of the charged C1 structures was explained by the Jahn–Teller or Pseudo-Jahn–Teller effect. This finding agrees with the available experimental X-ray structures of their metal complexes where electron density transfer from the metal can be expected. Hence, the membrane permeability of metal sandwich-structure complexes possessing antimicrobial activities is modulated by the conformational changes. [ABSTRACT FROM AUTHOR]

Fusarium proliferatum and Fusarium fujikuroi are the causative pathogens of stem rot in red-fleshed dragon fruit (Hylocereus polyrhizus). Both species are toxigenic fungi that produce several mycotoxins, including fumonisin B1 (FB1), moniliformin (MON), and beauvericin (BEA). These mycotoxins exert phytotoxic effects and are involved in pathogenesis in the host plants. In this study, we investigated the ability of F. proliferatum and F. fujikuroi to produce FB1, MON, and BEA. Polymerase chain reaction amplification using FUM1-specific primers detected the gene in all 44 isolates tested, indicating that all isolates produced FB1. Isolates of F. proliferatum and F. fujikuroi produced variable concentrations of FB1, ranging from 11.97-236.80 µg/g. MON and BEA were also produced at 0.48-174.84 µg/g and 0.28-70.02 µg/g, respectively by isolates of F. proliferatum and F. fujikuroi. These results suggest that the three mycotoxins play roles in stem rot disease development and symptom manifestation, as all isolates tested were pathogenic and led to stem rot in H. polyrhizus. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA) is an emerging mycotoxin produced by some species of Fusarium genera that widely contaminates food and feed. Gentiana lutea is a protected medicinal plant known for its antioxidant and anti-inflammatory properties, which are attributed to its rich content of bioactive compounds. In order to evaluate the beneficial effects of G. lutea flower against BEA cytotoxicity, the aim of this study is to evaluate changes in protein expression after Jurkat cell exposure through a proteomics approach. To carry out the experiment, cells were exposed to intestinally digested G. lutea flower alone or in combination with the BEA standard (100 nM) over 7 days. Differentially expressed proteins were statistically evaluated (p < 0.05), revealing a total of 172 proteins with respect to the control in cells exposed to the BEA standard, 145 proteins for G. lutea alone, and 139 proteins when exposing the cells to the combined exposure. Bioinformatic analysis revealed processes implicated in mitochondria, ATP-related activity, and RNA binding. After careful analysis of differentially expressed proteins, it was evident that G. lutea attenuated, in most cases, the negative effects of BEA. Furthermore, it decreased the presence of major oncoproteins involved in the modulation of immune function. [ABSTRACT FROM AUTHOR]

Mycotoxins, produced by fungi, frequently occur at different stages in the food supply chain between pre- and postharvest. Globally produced cereal crops are known to be highly susceptible to contamination, thus constituting a major public health concern. Among the encountered mycotoxigenic fungi in cereals, Fusarium spp. are the most frequent and produce both regulated (i.e., T-2 toxin, deoxynivalenol -DON-, zearalenone -ZEA-) and emerging (i.e., enniatins -ENNs-, beauvericin -BEA-) mycotoxins. In this study, we investigated the in vitro cytotoxic effects of regulated and emerging fusariotoxins on HepaRG cells in 2D and 3D models using undifferentiated and differentiated cells. We also studied the impact of ENN B1 and ENN B exposure on gene expression of HepaRG spheroids. Gene expression profiling pinpointed the differentially expressed genes (DEGs) and overall similar pathways were involved in responses to mycotoxin exposure. Complement cascades, metabolism, steroid hormones, bile secretion, and cholesterol pathways were all negatively impacted by both ENNs. For cholesterol biosynthesis, 23/27 genes were significantly down-regulated and could be correlated to a 30% reduction in cholesterol levels. Our results show the impact of ENNs on the cholesterol biosynthesis pathway for the first time. This finding suggests a potential negative effect on human health due to the essential role this pathway plays.

The Feature-based Molecular Networking (FBMN) is a well-known approach for mapping and identifying structures and analogues. However, in the absence of prior knowledge about the molecular class, assessing specific fragments and clusters requires time-consuming manual validation. This study demonstrates that combining FBMN and Mass Spec Query Language (MassQL) is an effective strategy for accelerating the decoding mass fragmentation pathways and identifying molecules with comparable fragmentation patterns, such as beauvericin and its analogues. To accomplish this objective, a spectral similarity network was built from ESI-MS/MS experiments of Fusarium oxysporum at various collision energies (CIDs) and paired with a MassQL search query for conserved beauvericin ions. FBMN analysis revealed that sodiated and protonated ions clustered differently, with sodiated adducts needing more collision energy and exhibiting a distinct fragmentation pattern. Based on this distinction, two sets of particular fragments were discovered for the identification of these hexadepsipeptides: ([M + H]+) m/z 134, 244, 262, and 362 and ([M + Na]+) m/z 266, 284 and 384. By using these fragments, MassQL accurately found other analogues of the same molecular class and annotated beauvericins that were not classified by FBMN alone. Furthermore, FBMN analysis of sodiated beauvericins at 70 eV revealed subclasses with distinct amino acid residues, allowing distinction between beauvericins (beauvericin and beauvericin D) and two previously unknown structural isomers with an unusual methionine sulfoxide residue. In summary, our integrated method revealed correlations between adduct types and fragmentation patterns, facilitated the detection of beauvericin clusters, including known and novel analogues, and allowed for the differentiation between structural isomers.

Wheat grains are susceptible to contamination with various natural mycotoxins including regulated and emerging mycotoxins. This study surveyed the natural presence of regulated mycotoxins, such as deoxynivalenol (DON) and zearalenone (ZEN), and emerging mycotoxins such as beauvericin (BEA), enniatins (ENNs such as ENA, ENA1, ENB, ENB1) and Alternaria mycotoxins (i.e., alternariol monomethyl ether (AME), alternariol (AOH), tenuazonic acid (TeA), tentoxin (TEN), and altenuene (ALT)) in wheat grains randomly collected from eight provinces across China in 2021. The results revealed that each wheat grain sample was detected with at least one type of mycotoxin. The detection rates of these mycotoxins ranged from 7.1% to 100%, with the average occurrence level ranging from 1.11 to 921.8 µg/kg. DON and TeA were the predominant mycotoxins with respect to both prevalence and concentration. Approximately 99.7% of samples were found to contain more than one toxin, and the co-occurrence of ten toxins (DON + ZEN + ENA + ENA1 + ENB + ENB1 + AME + AOH + TeA + TEN) was the most frequently detected combination. The dietary exposure to different mycotoxins among Chinese consumers aged 4–70 years was as follows: 0.592–0.992 µg/kg b.w./day for DON, 0.007–0.012 µg/kg b.w./day for ZEN, 0.0003–0.007 µg/kg b.w./day for BEA and ENNs, 0.223–0.373 µg/kg b.w./day for TeA, and 0.025–0.041 µg/kg b.w./day for TEN, which were lower than the health-based guidance values for each mycotoxin, with the corresponding hazard quotient (HQ) being far lower than 1, implying a tolerable health risk for Chinese consumers. However, the estimated dietary exposure to AME and AOH was in the range of 0.003–0.007 µg/kg b.w./day, exceeding the Threshold of Toxicological Concern (TTC) value of 0.0025 µg/kg b.w./day, demonstrating potential dietary risks for Chinese consumers. Therefore, developing practical control and management strategies is essential for controlling mycotoxins contamination in the agricultural systems, thereby ensuring public health. [ABSTRACT FROM AUTHOR]

A proper nutrition is crucial for children's healthy development. Regardless of the usual recommendations to follow a varied diet, some foods can be a source of toxic natural contaminants such as mycotoxins, potent secondary metabolites produced by filamentous fungi. In addition to the most well-known mycotoxins, many of which are subject to tight regulation regarding the maximum levels allowed in different types of food, there is a large group of mycotoxins, the so-called emerging mycotoxins, about which less knowledge has already been acquired, which have gradually been the target of interest from the scientific community due to their prevalence in most foodstuffs, particularly in cereals and cereal-based products. Alternariol and his metabolite alternariol mono-methyl ether, beauvericin, citrinin, culmorin, enniatins, ergot alkaloids, fusaproliferin, kojic acid, moniliformin, sterigmatocystin, tentoxin and tenuazonic acid are the most representative of them. The current review gathered the information of the last ten years that have been published on the levels of emerging mycotoxins in food products dedicated for infants and children. European Union countries are responsible for most of the reported studies, which showed levels that can reach hundreds of mg/kg. [ABSTRACT FROM AUTHOR]

Food and feed contamination by nonlegislated mycotoxins beauvericin (BEA) and enniatin B (ENB) is a worldwide health concern in the present. The principal objective of this work is to assess some of the existing protocols to discover the single nucleotide variants (SNVs) in transcriptomic data obtained by RNA-seq from Jurkat cells in vitro samples individually exposed to BEA and ENB at three concentration levels (1.5, 3 and 5 µM). Moreover, previous transcriptomic results will be compared with new findings obtained using a different protocol. SNVs rs201003509 in BEA exposed cells and the rs36045790 in ENB were found in the differentially expressed genes in all doses compared to controls by means of the Genome Analysis Toolkit (GATK) Best Practices workflow. SNV-RNA-seq complementary pipeline did not show any SNV. Concerning gene expression, discrepant results were found for 1.5 µM BEA exposed cells compared with previous findings. However, 354 overlapped differentially expressed genes (DEGs) were identified in the three ENB concentrations used, with 147 matches with respect to the 245 DEGs found in the previous results. In conclusion, the two discovery SNVs protocols based on variant calling from RNA-seq used in this work displayed very different results and there were SNVs found manually not identified by any pipeline. Additionally, the new gene expression analysis reported comparable but non identical DEGs to the previous transcriptomic results obtained from these RNA-seq data. Single-nucleotide variants discovery protocols in transcriptomic data by RNA-seq from Jurkat cells exposed to mycotoxins for the first time [ABSTRACT FROM AUTHOR]

Gluten-free cereal products have grown in popularity in recent years as they are perceived as "healthier" alternatives and can be safely consumed by celiac patients, and people with gluten intolerance or wheat allergies. Molds that produce mycotoxins contaminate cereal crops, posing a threat to global food security. Maximum levels have been set for certain mycotoxins in cereal flours; however, little is known about the levels of emerging mycotoxins in these flours. The aim of this study was to develop an efficient, sensitive, and selective method for the detection of four emerging (beauvericin and enniatins A1, B, and B1) and three regulated (aflatoxin B1, zearalenone, and deoxynivalenol) mycotoxins in gluten-free flours. Ultrasound-assisted matrix solid-phase dispersion was used in the extraction of these mycotoxins from flour samples. The validated method was utilized for the LC-MS/MS analysis of conventional and organic wholegrain oat and rice flours. Six of the seven target mycotoxins were detected in these samples. Multi-mycotoxin contamination was found in all flour types, particularly in conventional wholegrain oat flour. Despite the low detection frequency in rice flour, one sample was found to contain zearalenone at a concentration of 83.2 μg/kg, which was higher than the level set by the European Commission for cereal flours. The emerging mycotoxins had the highest detection frequencies; enniatin B was present in 53% of the samples at a maximum concentration of 56 μg/kg, followed by enniatin B1 and beauvericin, which were detected in 46% of the samples, and at levels reaching 21 μg/kg and 10 μg/kg, respectively. These results highlight the need to improve the current knowledge and regulations on the presence of mycotoxins, particularly emerging ones, in gluten-free flours and cereal-based products. [ABSTRACT FROM AUTHOR]

Frequently reported occurrences of deoxynivalenol (DON), beauvericin (BEA), and, to a lesser extent, ochratoxin A (OTA) and citrinin (CIT) in ruminant feed or feedstuff could represent a significant concern regarding feed safety, animal health, and productivity. Inclusion of yeast cell wall-based mycotoxin adsorbents in animal feeds has been a common strategy to mitigate adverse effects of mycotoxins. In the present study, an in vitro approach combining adsorption isotherm models and bioassays was designed to assess the efficacy of yeast cell wall (YCW), yeast cell wall extract (YCWE), and a postbiotic yeast cell wall-based blend (PYCW) products at the inclusion rate of 0.5% (w/v) (ratio of adsorbent mass to buffer solution volume). The Hill's adsorption isotherm model was found to best describe the adsorption processes of DON, BEA, and CIT. Calculated binding potential for YCW and YCWE using the Hill's model exhibited the same ranking for mycotoxin adsorption, indicating that BEA had the highest adsorption rate, followed by DON and CIT, which was the least adsorbed. PYCW had the highest binding potential for BEA compared with YCW and YCWE. In contrast, the Freundlich isotherm model presented a good fit for OTA adsorption by all adsorbents and CIT adsorption by PYCW. Results indicated that YCW was the most efficacious for sequestering OTA, whereas YCWE was the least efficacious. PYCW showed greater efficacy at adsorbing OTA than CIT. All adsorbents exhibited high adsorption efficacy for BEA, with an overall percentage average of bound mycotoxin exceeding 60%, whereas moderate efficacies for the other mycotoxins were observed (up to 37%). Differences in adsorbent efficacy of each adsorbent significantly varied according to experimental concentrations tested for each given mycotoxin (p < 0.05). The cell viability results from the bioassay using a bovine mammary epithelial cell line (MAC-T) indicated that all tested adsorbents could potentially mitigate mycotoxin-related damage to bovine mammary epithelium. Results from our studies suggested that all tested adsorbents had the capacity to adsorb selected mycotoxins in vitro, which could support their use to mitigate their effects in vivo. [ABSTRACT FROM AUTHOR]

Enniatin B (ENN B) and Beauvericin (BEA) are cyclohexadepsipeptides that can be isolated from Fusarium and Beauveria bassiana, respectively. Both compounds are cytotoxic and ionophoric. In the present study, the mechanism of cell death induced by these compounds was investigated. Epidermal carcinoma-derived cell line KB-3-1 cells were treated with different concentrations of these compounds. The extracellular secretion of cathepsin B increased in a concentration-dependent manner, and the lysosomal staining by lysotracker red was reduced upon the treatment with any of the compounds. However, the extracellular secretion of cathepsin L and cathepsin D were not affected. Inhibition of cathepsin B with specific inhibitor CA074 significantly reduced the cytotoxic effect of both compounds, while inhibition of cathepsin D or cathepsin L did not influence the cytotoxic activities of both compounds. In vitro labelling of lysosomal cysteine cathepsins with Ethyl (2S, 3S)-epoxysuccinate-Leu-Tyr-Acp-Lys (Biotin)-NH2 (DCG04) was not affected in case of cathepsin L upon the treatment with both compounds, while it was significantly reduced in case of cathepsin B. In conclusion, ENN B and BEA increase lysosomal Ph, which inhibits delivery of cathepsin B from Golgi to lysosomes, thereby inducing cathepsin B release in cytosol, which activates caspases and hence the apoptotic pathway. [ABSTRACT FROM AUTHOR]

Emerging Fusarium mycotoxins beauvericin (BEA), enniatins (ENNs), and moniliformin (MON) are gaining increasing interest due to their wide presence especially in cereals and grain‐based products. In vitro and in vivo studies indicate that Fusarium mycotoxins can be implicated in reproductive disorders in animals. Of these mycotoxins, BEA may affect reproductive functions, impairing the development of oocytes in pigs and sheep. Studies show dramatic inhibitory effects of BEA and ENNA on bovine granulosa cell steroidogenesis. ENNs also inhibit boar sperm motility and cause detrimental effects on embryos in mice and pigs. Although little data are reported on reproductive effects of MON, in vitro studies show inhibitory effects of MON on Chinese hamster ovary cells. The present review aims to summarize the reproductive toxicological effects of emerging Fusarium mycotoxins BEA, ENNs, and MON on embryo development, ovarian function, and testicular function of animals. In vitro and in vivo toxicological data are reported although additional studies are needed for proper risk assessment. Emerging Fusarium mycotoxins beauvericin (BEA), enniatins (ENNs) and moniliformin (MON) are gaining increasing interest due to their wide presence especially in cereals and grain‐based products. In vitro and in vivo studies indicate that Fusarium mycotoxins can be implicated in reproductive disorders in animals. The present review summarizes the reproductive toxicological effects of emerging Fusarium mycotoxins BEA, ENNs and MON on embryo development, ovarian function and testicular function of animals, but additional studies are needed for proper risk assessment. [ABSTRACT FROM AUTHOR]

Cordyceps spp. are widely healthy foods around the world with several traditional uses and bio-functionalities. The chemical characterization of ethyl acetate–soluble extract of the entomopathogenic fungus Cordyceps tenuipes NBRC 111,630 afforded two new metabolites with 1,6-dioxaspiro[4.4]nonane motif, tenuipesone A (1) and tenuipesone B (2), along with four well-known metabolites (3–6). The elucidation of the chemical structures was carried out via extensive spectroscopic experiments including FTIR, HRMS, 1D-NMR, and 2D-NMR. The probable biosynthetic pathway of 1 and 2 was hypothesized. From the six isolates, beauvericin (6) exhibited antimicrobial activity against Bacillus subtilis and Staphylococcus aureus with respective MIC of 6.25 and 12.5 μM. Docking results exhibited that beauvericin (6) has significant binding affinities against MurE and HK proteins with ΔG = − 8.021 and − 8.585 kcal/mol, respectively. Key points: • Six compounds, including two new, were isolated from the entomopathogenic fungus Cordyceps tenuipes. • Plausible biosynthetic pathway of compounds 1, 2, 4, and 5 was hypothesized. • Beauvericin (6) exhibited significant antimicrobial activity against Bacillus subtilis and Staphylococcus aureus alongside binding affinities against MurE and HK proteins in MOE study. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA), Enniatin B (ENN B), and Ochratoxin A (OTA) are mycotoxins produced by fungi species. Their main effect on several organs and systems is associated with chronic exposure going from immunotoxicity, estrogenic disorders, and renal failure to cancer (in animals and humans). OTA belongs to Group 1 according to the International Agency for Research in Cancer (IARC) and it has legislated limited values; not happening for BEA nor ENN B. Exposure to mixtures of mycotoxins occurs through food intake in daily consumption. The aim of this study was to evaluate the implication of BEA, ENN B, and OTA individually and combined in producing cytotoxicity in cells for immunological studies and cancer cell lines (human leukemia cells (HL-60), fresh human peripheral blood mononuclear cells (PBMCs), and human breast cancer (MDA-MB-231) cells). Cells were treated for 4 h and 24 h at different concentrations of BEA, ENN B, and OTA, respectively. Viability assays were carried out by flow cytometry using DAPI (4′,6-diamindino-2-phenylindole, dihydrochloride) as a viability dye and the potential effects of synergism, addition, and antagonism were assessed through the Chou and Talalay method. Individual OTA treatment exerted the greatest cytotoxicity for PBMC cells (IC 50 0.5 μM) while ENN B for HL-60 (IC 50 0.25 μM) and MDA-MB-231 (IC 50 0.15 μM). In binary combination [ENN B + OTA] resulted in exerting the greatest cytotoxicity for HL-60 and MDA-MB-231 cells; while [BEA + OTA] in PBMC cells. The triple combination resulted in being highly cytotoxic for PBMC cells compared to HL-60 and MDA-MB-231 cells. In summary, PBMC cells were the most sensible cells for all three mycotoxins and the presence of OTA in any of the combinations had the greatest toxicity causing synergism as the most common cytotoxic effect. • Individual OTA treatment exerted the greatest cytotoxicity for PBMC cells; while ENN B for HL-60 and MDA-MB-231. • Mixture [ENN B + OTA] resulted in exerting the greatest cytotoxicity for HL-60 and MDA-MB-231 cells; while [BEA + OTA] in PBMC cells. • Synergistic effects in PBMC and MDA-MB231 cells was mainly revealed for mixtures of BEA, ENN B and OTA. • Mixtures of BEA, ENN B and OTA in HL-60 cells revealed mainly antagonism. [ABSTRACT FROM AUTHOR]

Beauvericin is a cyclic hexadepsipeptide produced as secondary metabolites of an entomopathogenic fungus, Beauveria bassiana that shown nematocidal, insecticidal and cytotoxic activities. Glyphodes pyloalis Walker is a destructive pest of mulberry trees that extensive feeding of larvae on the leaves, pile of excreta and transmission of viral diseases to silkworm are of its constraints on regional sericulture. Since sustainable and environmental friendly control of G. pyloalis is of importance, the current study aimed to produce beauvericin by culturing a native isolate of B. bassiana to Czapek medium and extract it by high performance liquid chromatography using RPC18 column. The extracted beauvericin was exposed to the 4th instar larvae of G. pyloalis through leaf dipping method to determine mortality and lethal concentrations. Results showed the LC 50 of 0.918 μg/ml of beauvericin against the larvae. The LC 30 concentration of beauvericin was nano-formulated and treated orally against G. pyloalis larvae to determine its possible effects on nutritional indices, digestive and antioxidative enzymes. Results showed the decreased level of nutritional indices and imposing the metabolic cost of the treated larvae compared to control. Digestive enzymes were also negatively influenced following larval feeding on the leaves treated by beauvericin except for α-glucosidase and lipase. Antioxidative enzymes were also affected in the treated larvae by beauvericin in that their activity significantly increased except for gluxcose-6-phosphate dehydrogenase. Results of the current study revealed the nano-formulation of beauvericin affected physiological performance of the larvae in a sublethal concentration. These results imply on potential of nano-formulated beauvericin to be used against G. pyloalis as a nature-based insecticide. [Display omitted] • Beauvericin was toxic against Glyphodes pyloalis larvae by LC 50 of 0.918 μg/ml. • Sub-lethal concentration of beauvericin decreased the level of nutritional indices. • Digestive enzymes were negatively influenced in the beauvericin-treated larvae. • The activity of antioxidative enzymes significantly incraesed after beauvericin treatment. [ABSTRACT FROM AUTHOR]

Fusarium isolates from highland areas in Malaysia were mostly recovered from two species of grasses, Elyhordeum montanense and Paspalum conjugatum. The isolates were grouped into four morphological groups. Based on TEF-1a sequences, morphotype 1 isolates were molecularly identified as F. graminearum species complex, morphotype 2 as F. venenatum, morphotype 3 as F. avenaceum and morphotype 4 as F. kyushuense. Restriction analysis of the Intergenic Spacer region showed high levels of genetic diversity of isolates in F. graminearum species complex and F. venenatum. For mycotoxin analysis, only F. avenaceum and F. kyushuense produced beauvericin and moniliformin (0.869 & 0.321 µg/kg, respectively). Zearalenone was produced by 32 isolates of F. graminearum species complex (0.002 - 0.437 µg/kg), two isolates of F. venenatum (0.006 - 0.014 µg/kg) and F. kyushuense (0.006 µg/kg). Only F. avenaceum isolate produced fumonisin B1 (0.001 µg/kg). The present study indicates the occurrence of Fusarium species commonly reported in highland areas in Malaysia where the weather is cooler and the temperature is lower than in the lowland areas. To our knowledge, this is the first report on the occurrence of phylogenetic species within F. graminearum species complex, F. venenatum, F. avenaceum and F. kyushuense in Malaysia. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA), cyclopiazonic acid (CPA), and sterigmatocystin (STC) are emerging mycotoxins. They appear as contaminants in food and animal feed, leading to economic losses and health risks. Human serum albumin (HSA) forms stable complexes with certain mycotoxins, including ochratoxins, alternariol, citrinin, and zearalenone. HSA binding can influence the toxicokinetics of xenobiotics, and albumin can also be considered and applied as a relatively cheap affinity protein. Therefore, we examined the potential interactions of BEA, CPA, and STC with HSA employing fluorescence spectroscopy, ultracentrifugation, ultrafiltration, and molecular modeling. Spectroscopic and ultracentrifugation studies demonstrated the formation of low-affinity BEA–HSA (Ka ≈ 103 L/mol) and moderately strong CPA–HSA and STC–HSA complexes (Ka ≈ 104 L/mol). In ultrafiltration experiments, CPA slightly displaced each site marker (warfarin, naproxen, and camptothecin) tested, while BEA and STC did not affect significantly the albumin binding of these drugs. Modeling studies suggest that CPA occupies Sudlow's site I, while STC binds to the Heme site (FA1) on HSA. Considering the interactions of CPA with the site markers, the CPA–HSA interaction may have toxicological importance. [ABSTRACT FROM AUTHOR]

Raw feed materials are often contaminated with mycotoxins, and co-occurrence of mycotoxins occurs frequently. A total of 250 samples i.e., rice bran and maize from Cambodia, Laos, Myanmar, and Thailand were analysed using state-of-the-art liquid chromatography-mass spectrometry (LC-MS/MS) for monitoring the occurrence of regulated, emerging, and masked mycotoxins. Seven regulated mycotoxins – aflatoxins, ochratoxin A, fumonisin B1, deoxynivalenol, zearalenone, HT-2, and T-2 toxin were detected as well as some emerging mycotoxins, such as beauvericin, enniatin type B, stachybotrylactam, sterigmatocystin, and masked mycotoxins, specifically zearalenone-14-glucoside, and zearalenone-16-glucoside. Aspergillus and Fusarium mycotoxins were the most prevalent compounds identified, especially aflatoxins and fumonisin B1 in 100% and 95% of samples, respectively. Of the emerging toxins, beauvericin and enniatin type B showed high occurrences, with more than 90% of rice bran and maize contaminated, whereas zearalenone-14-glucoside and zearalenone-16-glucoside were found in rice bran in the range of 56–60%. Regulated mycotoxins (DON and ZEN) were the most frequent mycotoxin combination with emerging mycotoxins (BEA and ENN type B) in rice bran and maize. This study indicates that mycotoxin occurrence and co-occurrence are common in raw feed materials, and it is critical to monitor mycotoxin levels in ASEAN's feedstuffs so that mitigation strategies can be developed and implemented. [ABSTRACT FROM AUTHOR]

Fusarium basal rot (FBR), caused by Fusarium spp., is a serious impediment for onion production. In the present study, the interaction of onion (Allium cepa) var. Takstar F1 with Allium‐derived isolates of the toxigenic species F. oxysporum and F. proliferatum was investigated at seedling and bulb stage. Using a set of isolates with distinct virulence profiles, we provide evidence that the outcome of FBR is driven by the phenology of onion. Reverse transcription‐quantitative PCR analysis revealed distinct expression of reliable marker genes for phenylalanine ammonia‐lyase (PAL1, PAL2), lipoxygenase (LOX2), chalcone synthase (CHS), anthocyanidin synthase (ANS) and pectin methylesterases (PME) during the infection of seedlings and bulbs. These defence‐related genes in seedlings were differentially expressed depending on the aggressiveness of Fusarium isolates. Despite these differential kinetics, the activated plant defence did not seem to be effective in protecting the seedlings from Fusarium infection and proliferation. Meanwhile, gene expression in the bulb organs correlated positively with FBR severity, indicating an ineffective defence response. Among the major metabolites of these Fusarium species, beauvericin was not toxic to either the seedlings or the bulbs, while fumonisin B1 appeared to be a virulence factor specific for the seedling stage. This points to differential roles of fumonisin B1 during an infection of F. proliferatum depending on the infected organ and the phenological stage of the onion host. We hypothesize that this variation, along with the differences within and between Fusarium species in terms of virulence and metabolism, contributes to the determination of disease outcome. [ABSTRACT FROM AUTHOR]

The production of beauvericin (BEA) by Fusarium oxysporum AB2 in liquid medium (SmF) was compared to that on solid medium (SSF) on inert support (polyurethane foam or PUF), using a previously optimised medium. The analysis included two different concentrations of the medium (1 × and 3 ×). Under SSF, the production of BEA (22.8 mg·L−1) was higher relative to SmF (0.8 mg·L−1). The production increased proportionally in the concentrated medium (3 ×) (65.3 mg·L−1); using the concentrated medium in SmF, the production of BEA was completely inhibited, although more biomass was produced. The peak of BEA production was reached on day 7 and remained stable until day 11; sustained production after several days has not been achieved in similar reports. The presence of BEA was corroborated by high-performance liquid chromatography (HPLC) and mass spectrometry. The BEA production profile is shown performing mixed cultures of Fusarium oxysporum AB2 and Epicoccum nigrum TORT using the same system, increasing the production of BEA up to 84.6 mg·L−1. We propose SSF using polyurethane foam (PUF) as a solid support as a new culture system for obtaining secondary metabolites such as BEA. [ABSTRACT FROM AUTHOR]

The taxonomy of the genus Fusarium has been in a flux because of ambiguous circumscription of species-level identification based on morphotaxonomic criteria. In this study, multigene phylogeny was conducted to resolve the evolutionary relationships of 88 Indian Fusarium isolates based on the internal transcribed spacer region, 28S large subunit, translation elongation factor 1-alpha, RNA polymerase second largest subunit, beta-tubulin and calmodulin gene regions. Fusarium species are well known to produce metabolites such as beauvericin (BEA) and enniatins. These identified isolates were subjected to fermentation in Fusarium-defined media for BEA production and tested using TLC, HPLC and HRMS. Among 88 isolates studied, 50 were capable of producing BEA, which varied from 0.01 to 15.82 mg/g of biomass. Fusarium tardicrescens NFCCI 5201 showed maximum BEA production (15.82 mg/g of biomass). The extract of F. tardicrescens NFCCI 5201 showed promising antibacterial activity against Staphylococcus aureus MLS16 MTCC 2940 and Micrococcus luteus MTCC 2470 with MIC of 62.5 and 15.63 µg/mL, respectively. Similarly, the F. tardicrescens NFCCI 5201 extract in potato dextrose agar (40 µg/mL) exhibited antifungal activity in the food poison technique against plant pathogenic and other fungi, Rhizoctonia solani NFCCI 4327, Sclerotium rolfsii NFCCI 4263, Geotrichum candidum NFCCI 3744 and Pythium sp. NFCCI 3482, showing % inhibition of 84.31, 49.76, 38.22 and 35.13, respectively. The antibiotic effect was found to synergize when Fusarium extract and amphotericin B (20 µg/mL each in potato dextrose agar) were used in combination against Rhizopus sp. NFCCI 2108, Sclerotium rolfsii NFCCI 4263, Bipolaris sorokiniana NFCCI 4690 and Absidia sp. NFCCI 2716, showing % inhibition of 50.35, 79.37, 48.07 and 76.72, respectively. The extract also showed satisfactory dose-dependent DPPH radical scavenging activity with an IC50 value of 0.675 mg/mL. This study reveals the correct identity of the Indian Fusarium isolates based on multigene phylogeny and also throws light on BEA production potential, suggesting their possible applicability in the medicine, agriculture and industry. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA) is a well-known mycotoxin produced by many fungi, including Beaveria bassiana. The purpose of this study was to evaluate the in vitro distribution and metabolism characteristics as well as the in vivo pharmacokinetic (PK) profile of BEA. The in vitro metabolism studies of BEA were performed using rat, dog, mouse, monkey and human liver microsomes, cryopreserved hepatocytes and plasma under conditions of linear kinetics to estimate the respective elimination rates. Additionally, LC-UV-MSn (n = 1~2) was used to identify metabolites in human, rat, mouse, dog and monkey liver microsomes. Furthermore, cytochrome P450 (CYP) reaction phenotyping was carried out. Finally, the absolute bioavailability of BEA was evaluated by intravenous and oral administration in rats. BEA was metabolically stable in the liver microsomes and hepatocytes of humans and rats; however, it was a strong inhibitor of midazolam 1′-hydroxylase (CYP3A4) and mephenytoin 4′-hydroxylase (CYP2C19) activities in human liver microsomes. The protein binding fraction values of BEA were >90% and the half-life (T1/2) values of BEA were approximately 5 h in the plasma of the five species. The absolute bioavailability was calculated to be 29.5%. Altogether, these data indicate that BEA has great potential for further development as a drug candidate. Metabolic studies of different species can provide important reference values for further safety evaluation. [ABSTRACT FROM AUTHOR]

The European Food Safety Authority is currently evaluating the risks related to the presence of emerging mycotoxins in food and feeds. The aim of this study was to investigate the role of soil fertility, resulting from different nitrogen fertilization rates, on the contamination of regulated mycotoxins and emerging fungal metabolites in maize grains. The trial was carried out in the 2012–2013 growing seasons as part of a long-term (20-year) experimental platform area in North-West Italy, where five different N rates, ranging from 0 to 400 kg N ha−1, were applied to maize each year. Maize samples were analyzed by means of a dilute-and-shoot multi-mycotoxin LC-MS/MS method, and more than 25 of the most abundant mycotoxins and fungal metabolites were detected. Contamination by fumonisins and other fungal metabolites produced by Fusarium spp. of the section Liseola was observed to have increased in soils that showed a poor fertility status. On the other hand, an overload of nitrogen fertilization was generally associated with higher deoxynivalenol and zearalenone contamination in maize kernels, as well as a higher risk of other fungal metabolites produced by Fusarium spp. sections Discolor and Roseum. A balanced application of N fertilizer, in accordance with maize uptake, generally appears to be the best solution to guarantee an overall lower contamination by regulated mycotoxins and emerging fungal metabolites. [ABSTRACT FROM AUTHOR]

Many recent articles feature research on the Fusarium tricinctum species complex (FTSC), and their authors present different ideas on how the isolates of this species complex can be identified at the species level. In previous studies, our aim was to investigate the phylogeny of FTSC strains, which researchers have morphologically identified as Fusarium avenaceum, Fusarium arthrosporioides, and Fusarium anguioides. In the current study, our phylogenetic maximum parsimony and likelihood analyses of the DNA sequences of the translation elongation factor 1-alpha (TEF1) and combined sequences of TEF1 and beta-tubulin (TUB2) supported the existence of at least four main groups among these strains. Main Group I mainly contains F. avenaceum strains, while Main Group II contains two subgroups, one of which primarily includes F. arthrosporioides strains, and the other mainly includes European F. anguioides strains. Main Group III contains strains from different plants that originated from Asia, including two F. anguioides strains. F. avenaceum strains, which are mostly isolated from different trees, form Main Group IV. A fifth group (Main Group V) was only supported by TEF1 sequences. The main groups previously found by us based on TUB2 sequences could be connected to the new species of the FTSC, which were identified based on TEF1 sequences. In addition, we found strains that significantly differ from Main Groups I-V, and we grouped some of them as single, intermediate, or sister groups. All of the main groups of the present work, and some single and intermediate strains, may represent different species of the FTSC, while the two subgroups of Main Group II constitute intraspecific variation. Regardless of whether they belonged to the main groups, all the analysed strains were able to form different enniatins and 2-amino-14,16-dimethyloctadecan-3-ol, but did not produce beauvericin. [ABSTRACT FROM AUTHOR]

Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract (from the pulp) against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach. The cells were added with mycotoxins at a concentration of 100 nmol/L per mycotoxin and pumpkin carotenoid extract at 500 nmol/L. For control we used only vehicle solvent (cell control) or vehicle solvent with pumpkin extract (extract control). After two hours of exposure, samples were analysed with HPLC-ESI-QTOF-MS. Metabolites were identified against the Metlin database. The proinflammatory arachidonic acid metabolite eoxin (14,15-LTE4) showed lower abundance in ZEA and BEA+OTA+ZEA-treated cultures that also received the pumpkin extract than in cultures that were not treated with the extract. Another marker of inflammation, prostaglandin D2-glycerol ester, was only found in cultures treated with OTA+ZEA and BEA+OTA+ZEA but not in the ones that were also treated with the pumpkin extract. Furthermore, the concentration of the pumpkin extract metabolite dihydromorelloflavone significantly decreased in the presence of mycotoxins. In conclusion, the pumpkin extract showed protective activity against cellular inflammation triggered by mycotoxins thanks to the properties pertinent to flavonoids contained in the pulp.

Beauveria bassiana is an important entomopathogenic fungus that is widely used as a bioinsecticide around the world. Conidia production is a critical step in the production of high-quality bioinsecticide. This study investigated three liquid culture mediums and five combinations of solid substrates to enhance conidia production by B. bassiana. The fungus was isolated from infected insects in the cocoa plantation of PT. Perkebunan Nusantara XII in Kediri, East Java, Indonesia. The three culture mediums were malt extract broth (MB), potato dextrose broth (PDB), and yeast and malt extract broth (YMB). Five combinations of solid substrate were used: 100% rice, 100% maize, 75%:25% rice:maize, 50%:50% rice:maize, and 25%:75% rice:maize. The biphasic system was used in this study, in which the fungus was first grown under submerged conditions and then was allowed to conidiate in solid-state conditions. The data showed that PDB was the optimum culture medium to produce blastophore and beauvericin, the active compound that acts as a mycoinsecticide. In the selection test, 100% rice was the optimum solid substrate to produce high amounts of conidia, and the consistency and production tests yielded the same results, with conidia counts of 1.93x109, 1.78x109, and 2.08x109, respectively. In a rice storability test, B. bassiana conidia numbers remained stable for up to 105 days of storage at room temperature. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA), a food-borne mycotoxin metabolite derived from the fungus Beauveria Bassiana, is proven to exhibit high hepatotoxicity. However, the molecular mechanism underlying BEA-induced liver damage is not fully understood. Herein, the effect of Nrf2 nuclear translocation-induced by BEA in hepatocytes was investigated. CCK8 solution was used to determine the appropriate concentrations of BEA (0, 1, 1.5 and 2 μmol/L), and BRL3A cells were then exposed to different concentrations of BEA for 12 h. Our results reveal that BEA exposure is associated with high cytotoxicity, lowered cell viability, damaged cellular morphology, and increased apoptosis rate. BEA could lead to oxidative damage through the overproduction of ROS and unbalanced redox, trigger the activation of Nrf2 signaling pathway and Nrf2 nuclear translocation for transcriptional activation of downstream antioxidative genes. Additionally, BEA treatment upregulated the expression of autophagy-related proteins (LC3, p62, Beclin1, and ATG5) indicating a correlation between Nrf2 activation and autophagy, which warrants further studies. Furthermore, ML385, an Nrf2 inhibitor, partially ameliorated BEA-induced cell injury while CDDO, an Nrf2 activator, aggravated liver damage. The present study emphasizes the role of Nrf2 nuclear translocation in BEA-induced oxidative stress associated with the hepatotoxic nature of BEA. [ABSTRACT FROM AUTHOR]