Ten decadal advances in fungal biology leading towards human well-being.

Fungi are an understudied resource possessing huge potential for developing products that can greatly improve human well-being. In the current paper, we highlight some important discoveries and developments in applied mycology and interdisciplinary Life Science research. These examples concern recently introduced drugs for the treatment of infections and neurological diseases; application of -OMICS techniques and genetic tools in medical mycology and the regulation of mycotoxin production; as well as some highlights of mushroom cultivaton in Asia. Examples for new diagnostic tools in medical mycology and the exploitation of new candidates for therapeutic drugs, are also given. In addition, two entries illustrating the latest developments in the use of fungi for biodegradation and fungal biomaterial production are provided. Some other areas where there have been and/or will be significant developments are also included. It is our hope that this paper will help realise the importance of fungi as a potential industrial resource and see the next two decades bring forward many new fungal and fungus-derived products.

Role of Tocochromanols in Tolerance of Cereals to Biotic Stresses: Specific Focus on Pathogenic and Toxigenic Fungal Species.

Fungal pathogens capable of producing mycotoxins are one of the main threats to the cultivation of cereals and the safety of the harvested kernels. Improving the resistance of crops to fungal disease and accumulation of mycotoxins is therefore a crucial issue. Achieving this goal requires a deep understanding of plant defense mechanisms, most of them involving specialized metabolites. However, while numerous studies have addressed the contribution of phenylpropanoids and carotenoids to plant chemical defense, very few have dealt with tocochromanols. Tocochromanols, which encompass tocopherols and tocotrienols and constitute the vitamin E family, are widely distributed in cereal kernels; their biosynthetic pathway has been extensively studied with the aim to enrich plant oils and combat vitamin E deficiency in humans. Here we provide strong assumptions arguing in favor of an involvement of tocochromanols in plant-fungal pathogen interactions. These assumptions are based on both direct effects resulting from their capacity to scavenge reactive oxygen species, including lipid peroxyl radicals, on their potential to inhibit fungal growth and mycotoxin yield, and on more indirect effects mainly based on their role in plant protection against abiotic stresses.

Computational Strategy for Minimizing Mycotoxins in Cereal Crops: Assessment of the Biological Activity of Compounds Resulting from Virtual Screening.

Cereal crops are frequently affected by toxigenic Fusarium species, among which the most common and worrying in Europe are Fusarium graminearum and Fusarium culmorum. These species are the causal agents of grain contamination with type B trichothecene (TCTB) mycotoxins. To help reduce the use of synthetic fungicides while guaranteeing low mycotoxin levels, there is an urgent need to develop new, efficient and environmentally-friendly plant protection solutions. Previously, F. graminearum proteins that could serve as putative targets to block the fungal spread and toxin production were identified and a virtual screening undertaken. Here, two selected compounds, M1 and M2, predicted, respectively, as the top compounds acting on the trichodiene synthase, a key enzyme of TCTB biosynthesis, and the 24-sterol-C-methyltransferase, a protein involved in ergosterol biosynthesis, were submitted for biological tests. Corroborating in silico predictions, M1 was shown to significantly inhibit TCTB yield by a panel of strains. Results were less obvious with M2 that induced only a slight reduction in fungal biomass. To go further, seven M1 analogs were assessed, which allowed evidencing of the physicochemical properties crucial for the anti-mycotoxin activity. Altogether, our results provide the first evidence of the promising potential of computational approaches to discover new anti-mycotoxin solutions.

Naturally occurring phenolic compounds as promising antimycotoxin agents: Where are we now?

Mycotoxins are metabolites produced by molds that contaminate food commodities, are harmful to both humans and animals, as well as cause economic losses. Many countries have set regulatory limits and strict thresholds to control the level of mycotoxins in food and feedstuffs. New technologies and strategies have been developed to inhibit toxigenic fungal invasion and to decontaminate mycotoxins. However, many of these strategies do not sufficiently detoxify mycotoxins and leave residual toxic by-products. This review focuses on the use of phenolic compounds obtained from botanical extracts as promising bioagents to inhibit fungal growth and/or to limit mycotoxin yields. The mechanism of these botanicals, legislation concerning their use, and their safety are also discussed. In addition, recent strategies to overcome stability and solubility constraints of phenolic compounds to be used in food and feed stuffs are also mentioned.

Ammoides pusilla Essential Oil: A Potent Inhibitor of the Growth of Fusarium avenaceum and Its Enniatin Production.

Enniatins are mycotoxins produced by Fusarium species contaminating cereals and various agricultural commodities. The co-occurrence of these mycotoxins in large quantities with other mycotoxins such as trichothecenes and the possible synergies in toxicity could lead to serious food safety problems. Using the agar dilution method, Ammoides pusilla was selected among eight Tunisian plants for the antifungal potential of its essential oil (EO) on Fusarium avenaceum mycelial growth and its production of enniatins. Two EO batches were produced and analyzed by GC/MS-MS. Their activities were measured using both contact assays and fumigant tests (estimated IC50 were 0.1 µL·mL-1 and 7.6 µL·L-1, respectively). The A. pusilla EOs and their volatiles inhibited the germination of spores and the mycelial growth, showing a fungistatic but not fungicidal activity. The accumulation of enniatins was also significantly reduced (estimated IC50 were 0.05 µL·mL-1 for the contact assays and 4.2 µL·L-1 for the fumigation assays). The most active batch of EO was richer in thymol, the main volatile compound found. Thymol used as fumigant showed a potent fungistatic activity but not a significant antimycotoxigenic activity. Overall, our data demonstrated the bioactivity of A. pusilla EO and its high potential to control F. avenaceum and its enniatins production in agricultural commodities.

Screening of Wood/Forest and Vine By-Products as Sources of New Drugs for Sustainable Strategies to Control Fusarium graminearum and the Production of Mycotoxins.

Fusarium graminearum is a fungal pathogen that can colonize small-grain cereals and maize and secrete type B trichothecene (TCTB) mycotoxins. The development of environmental-friendly strategies guaranteeing the safety of food and feed is a key challenge facing agriculture today. One of these strategies lies on the promising capacity of products issued from natural sources to counteract crop pests. In this work, the in vitro efficiency of sixteen extracts obtained from eight natural sources using subcritical water extraction at two temperatures was assessed against fungal growth and TCTB production by F. graminearum. Maritime pine sawdust extract was shown to be extremely efficient, leading to a significant inhibition of up to 89% of the fungal growth and up to 65% reduction of the mycotoxin production by F. graminearum. Liquid chromatography/mass spectrometry analysis of this active extract revealed the presence of three families of phenolics with a predominance of methylated compounds and suggested that the abundance of methylated structures, and therefore of hydrophobic compounds, could be a primary factor underpinning the activity of the maritime pine sawdust extract. Altogether, our data support that wood/forest by-products could be promising sources of bioactive compounds for controlling F. graminearum and its production of mycotoxins.

Evolution of Fusarium tricinctum and Fusarium avenaceum mitochondrial genomes is driven by mobility of introns and of a new type of palindromic microsatellite repeats.

BACKGROUND: Increased contamination of European and Asian wheat and barley crops with "emerging" mycotoxins such as enniatins or beauvericin, produced by Fusarium avenaceum and Fusarium tricinctum, suggest that these phylogenetically close species could be involved in future food-safety crises. RESULTS: The mitochondrial genomes of F. tricinctum strain INRA104 and F. avenaceum strain FaLH27 have been annotated. A comparative analysis was carried out then extended to a set of 25 wild strains. Results show that they constitute two distinct species, easily distinguished by their mitochondrial sequences. The mitochondrial genetic variability is mainly located within the intergenic regions. Marks of variations show they have evolved (i) by Single Nucleotide Polymorphisms (SNPs), (ii) by length variations mediated by insertion/deletion sequences (Indels), and (iii) by length mutations generated by DNA sliding events occurring in mononucleotide (A)n or (T)n microsatellite type sequences arranged in a peculiar palindromic organization. The optionality of these palindromes between both species argues for their mobility. The presence of Indels and SNPs in palindrome neighbouring regions suggests their involvement in these observed variations. Moreover, the intraspecific and interspecific variations in the presence/absence of group I introns suggest a high mobility, resulting from several events of gain and loss during short evolution periods. Phylogenetic analyses of intron orthologous sequences suggest that most introns could have originated from lateral transfers from phylogenetically close or distant species belonging to various Ascomycota genera and even to the Basidiomycota fungal division. CONCLUSIONS: Mitochondrial genome evolution between F. tricinctum and F. avenaceum is mostly driven by two types of mobile genetic elements, implicated in genome polymorphism. The first one is represented by group I introns. Indeed, both genomes harbour optional (inter- or intra-specifically) group I introns, all carrying putatively functional hegs, arguing for a high mobility of these introns during short evolution periods. The gain events were shown to involve, for most of them, lateral transfers between phylogenetically distant species. This study has also revealed a new type of mobile genetic element constituted by a palindromic arrangement of (A) n and (T) n microsatellite sequences whose presence was related to occurrence of SNPs and Indels in the neighbouring regions.

Efficiency of Hydroxycinnamic Phenolic Acids to Inhibit the Production of Ochratoxin A by Aspergillus westerdijkiae and Penicillium verrucosum.

Ochratoxin A (OTA) is one of the worldwide most important mycotoxins in terms of health and agroeconomic consequences. With the aim to promote the use of phytochemicals as alternatives to synthetic fungicides, the effect of hydroxycinnamic acids on the fungal growth and OTA yield by two major OTA-producing species was investigated. After a first step dedicated to the definition of most suitable culture conditions, the impact of 0.5 mM ferulic (FER), p-coumaric (COUM), caffeic and chlorogenic acids was evaluated on Aspergillus westerdijkiae and Penicillium verrucosum. Whereas no fungal growth reduction was observed regardless of the phenolic acid and fungal isolate, our results demonstrated the capacity of FER and COUM to inhibit OTA production. The most efficient compound was FER that led to a 70% reduction of OTA yielded by P. verrucosum and, although not statistically significant, a 35% inhibition of OTA produced by A. westerdijkiae. To further investigate the bioactivity of FER and COUM, their metabolic fate was characterized in fungal broths. The capacity of P. verrucosum to metabolize FER and COUM through a C2-clivage type degradation was demonstrated. Overall, our data support the potential use of FER to prevent OTA contamination and reduce the use of synthetic pesticides.

Optimizing 1D 1H-NMR profiling of plant samples for high throughput analysis: extract preparation, standardization, automation and spectra processing.

INTRODUCTION: Proton nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomic profiling has a range of applications in plant sciences. OBJECTIVES: The aim of the present work is to provide advice for minimizing uncontrolled variability in plant sample preparation before and during NMR metabolomic profiling, taking into account sample composition, including its specificity in terms of pH and paramagnetic ion concentrations, and NMR spectrometer performances. METHODS: An automation of spectrometer preparation routine standardization before NMR acquisition campaign was implemented and tested on three plant sample sets (extracts of durum wheat spikelet, Arabidopsis leaf and root, and flax leaf, root and stem). We performed 1H-NMR spectroscopy in three different sites on the wheat sample set utilizing instruments from two manufacturers with different probes and magnetic field strengths. The three collections of spectra were processed separately with the NMRProcFlow web tool using intelligent bucketing, and the resulting buckets were subjected to multivariate analysis. RESULTS: Comparability of large- (Arabidopsis) and medium-size (flax) datasets measured at 600 MHz and from the wheat sample set recorded at the three sites (400, 500 and 600 MHz) was exceptionally good in terms of spectral quality. The coefficient of variation of the full width at half maximum (FWHM) and the signal-to-noise ratio (S/N) of two selected peaks was comprised between 5 and 10% depending on the size of sample set and the spectrometer field. EDTA addition improved citrate and malate resonance patterns for wheat sample sets. A collection of 22 samples of wheat spikelet extracts was used as a proof of concept and showed that the data collected at the three sites on instruments of different field strengths and manufacturers yielded the same discrimination pattern of the biological groups. CONCLUSION: Standardization or automation of several steps from extract preparation to data reduction improves data quality for small to large collections of plant samples of different origins.

Priming to protect maize from Fusarium verticillioides and its fumonisin accumulation.

BACKGROUND: Systemic infection through the seed is one of the routes used by the mycotoxinogenic pathogen Fusarium verticillioides for colonizing maize plants. The prohibition of the use of most chemical fungicides by the EU has promoted research on plant resistance inducers as an effective and sustainable alternative. Induction of a priming state in maize seeds might affect their susceptibility to contamination and accumulation of fumonisins. This state by application of a natural fertilizer called Chamae on maize seeds, was investigated in two varieties to control the colonization by the fungus and the accumulation of fumonisins B1 , B2 and B3 , germinating seeds, dead plants and yield. RESULTS: After inoculation of F. verticillioides on germinating seeds, the colonization by the fungus and the accumulation of fumonisins were significantly lower in seedlings coming from treated seeds, but a significant number of plants stopped their development by necrosis. In a field trial, the 0.01% (v/v) application dilution showed a lower plant density, although the level of biomass at harvest was not affected. CONCLUSION: The priming state contributed to the control of F. verticillioides development from seed infection and fumonisin accumulation in the early stage of plant growth, without affecting the final crop yield, and could reduce fungicide use and environmental contamination. © 2018 Society of Chemical Industry.

Mycotoxin Biosynthesis and Central Metabolism Are Two Interlinked Pathways in Fusarium graminearum, as Demonstrated by the Extensive Metabolic Changes Induced by Caffeic Acid Exposure.

Fusarium graminearum is a major plant pathogen that causes devastating diseases of cereals and produces type B trichothecene (TCTB) mycotoxins in infected grains. A comprehensive understanding of the molecular and biochemical mechanisms underlying the regulation of TCTB biosynthesis is required for improving strategies to control the TCTB contamination of crops and ensuring that these strategies do not favor the production of other toxic metabolites by F. graminearum Elucidation of the association of TCTB biosynthesis with other central and specialized processes was the focus of this study. Combined 1H nuclear magnetic resonance (1H NMR) and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS) analyses were used to compare the exo- and endometabolomes of F. graminearum grown under toxin-inducing and -repressing caffeic acid conditions. Ninety-five metabolites were putatively or unambiguously identified, including 26 primary and 69 specialized metabolites. Our data demonstrated that the inhibition of TCTB production induced by caffeic acid exposure was associated with significant changes in the secondary and primary metabolism of F. graminearum, although the fungal growth was not affected. The main metabolic changes were an increase in the accumulation of several polyketides, including toxic ones, alterations in the tricarboxylic organic acid cycle, and modifications in the metabolism of several amino acids and sugars. While these findings provide insights into the mechanisms that govern the inhibition of TCTB production by caffeic acid, they also demonstrate the interdependence between the biosynthetic pathway of TCTB and several primary and specialized metabolic pathways. These results provide further evidence of the multifaceted role of TCTB in the life cycle of F. graminearumIMPORTANCEFusarium graminearum is a major plant pathogen that causes devastating diseases of cereal crops and produces type B trichothecene (TCTB) mycotoxins in infected grains. The best way to restrict consumer exposure to TCTB is to limit their production before harvest, which requires increasing the knowledge on the mechanisms that regulate their biosynthesis. Using a metabolomics approach, we investigated the interconnection between the TCTB production pathway and several fungal metabolic pathways. We demonstrated that alteration in the TCTB biosynthetic pathway can have a significant impact on other metabolic pathways, including the biosynthesis of toxic polyketides, and vice versa. These findings open new avenues for identifying fungal targets for the design of molecules with antimycotoxin properties and therefore improving sustainable strategies to fight against diseases caused by F. graminearum Our data further demonstrate that analyses should consider all fungal toxic metabolites rather than the targeted family of mycotoxins when assessing the efficacy of control strategies.

Characterization of GMO or glyphosate effects on the composition of maize grain and maize-based diet for rat feeding.

INTRODUCTION: In addition to classical targeted biochemical analyses, metabolomic analyses seem pertinent to reveal expected as well as unexpected compositional differences between plant genetically modified organisms (GMO) and non-GMO samples. Data previously published in the existing literature led to divergent conclusions on the effect of maize transgenes on grain compositional changes and feeding effects. Therefore, a new study examining field-grown harvested products and feeds derived from them remains useful. OBJECTIVES: Our aim was to use a metabolomics approach to characterize grain and grain-based diet compositional changes for two GMO events, one involving Bacillus thuringiensis toxin to provide insect resistance and the other one conferring herbicide tolerance by detoxification of glyphosate. We also investigated the potential compositional modifications induced by the use of a glyphosate-based herbicide on the transgenic line conferring glyphosate tolerance. RESULTS: The majority of statistically significant differences in grain composition, evidenced by the use of 1H-NMR profiling of polar extracts and LC-ESI-QTOF-MS profiling of semi-polar extracts, could be attributed to the combined effect of genotype and environment. In comparison, transgene and glyphosate effects remained limited in grain for the compound families studied. Some but not all compositional changes observed in grain were also detected in grain-based diets formulated for rats. CONCLUSION: Only part of the data previously published in the existing literature on maize grains of plants with the same GMO events could be reproduced in our experiment. All spectra have been deposited in a repository freely accessible to the public. Our grain and diet characterization opened the way for an in depth study of the effects of these diets on rat health.

Yeast and bacteria from ensiled high moisture maize grains as potential mitigation agents of fumonisin B1.

BACKGROUND: Fumonisin B1 (FB1 ) is a mycotoxin produced by several Fusarium species and is a very common contaminant of maize-based food and feed throughout the world. The selection and use of FB1 -degrading microorganisms appears as a promising alternative to cope with the problem of toxicity towards humans and livestock. High moisture maize grain silage, which is based on natural maize fermentation, could be an interesting reservoir of such microorganisms. RESULTS: Using an in vitro simulated silage model with FB1 naturally contaminated grains, we demonstrated a significant raw decrease in FB1 during ensiling process ascribed to biodegradation mechanisms. A panel of 98 bacteria and yeasts were isolated from this matrix and selected for their ability to use FB1 as the sole source of C and N. For nine of them, the ability to degrade FB1 in vitro was evidenced. Notably, two bacteria identified as Lactobacillus sp. were highlighted for their efficient FB1 -degrading capacity and production of hydrolysed FB1 as intermediate degradation metabolite. CONCLUSION: Fermentation of high moisture maize grain contaminated with FB1 leads to a significant reduction of the toxin and allows the isolation of FB1 -degrading microorganisms that could further be used as FB1 decontaminating agents. © 2016 Society of Chemical Industry.

Effects of Phenolic Acids on the Growth and Production of T-2 and HT-2 Toxins by Fusarium langsethiae and F. sporotrichioides.

The effect of natural phenolic acids was tested on the growth and production of T-2 and HT-2 toxins by Fusarium langsethiae and F. sporotrichioides, on Mycotoxin Synthetic medium. Plates treated with 0.5 mM of each phenolic acid (caffeic, chlorogenic, ferulic and p-coumaric) and controls without phenolic acid were incubated for 14 days at 25 °C. Fungal biomass of F. langsethiae and F. sporotrichioides was not reduced by the phenolic acids. However, biosynthesis of T-2 toxin by F. langsethiae was significantly reduced by chlorogenic (23.1%) and ferulic (26.5%) acids. Production of T-2 by F. sporotrichioides also decreased with ferulic acid by 23% (p < 0.05). In contrast, p-coumaric acid significantly stimulated the production of T-2 and HT-2 toxins for both strains. A kinetic study of F. langsethiae with 1 mM ferulic acid showed a significant decrease in fungal biomass, whereas T-2 production increased after 10 days of incubation. The study of gene expression in ferulic supplemented cultures of F. langsethiae revealed a significant inhibition for Tri5, Tri6 and Tri12 genes, while for Tri16 the decrease in gene expression was not statistically significant. Overall, results indicated that phenolic acids had a variable effect on fungal growth and mycotoxin production, depending on the strain and the concentration and type of phenolic acid assayed.

Coupling of transcriptional response to oxidative stress and secondary metabolism regulation in filamentous fungi.

To survive sudden and potentially lethal changes in their environment, filamentous fungi must sense and respond to a vast array of stresses, including oxidative stresses. The generation of reactive oxygen species, or ROS, is an inevitable aspect of existence under aerobic conditions. In addition, in the case of fungi with pathogenic lifestyles, ROS are produced by the infected hosts and serve as defense weapons via direct toxicity, as well as effectors in fungal cell death mechanisms. Filamentous fungi have thus developed complex and sophisticated responses to evade oxidative killing. Several steps are determinant in these responses, including the activation of transcriptional regulators involved in the control of the antioxidant machinery. Gathering and integrating the most recent advances in knowledge of oxidative stress responses in fungi are the main objectives of this review. Most of the knowledge coming from two models, the yeast Saccharomyces cerevisiae and fungi of the genus Aspergillus, is summarized. Nonetheless, recent information on various other fungi is delivered when available. Finally, special attention is given on the potential link between the functional interaction between oxidative stress and secondary metabolism that has been suggested in recent reports, including the production of mycotoxins.

Metabolomics to Decipher the Chemical Defense of Cereals against Fusarium graminearum and Deoxynivalenol Accumulation.

Fusarium graminearum is the causal agent of Fusarium head blight (FHB) and Gibberella ear rot (GER), two devastating diseases of wheat, barley, and maize. Furthermore, F. graminearum species can produce type B trichothecene mycotoxins that accumulate in grains. Use of FHB and GER resistant cultivars is one of the most promising strategies to reduce damage induced by F. graminearum. Combined with genetic approaches, metabolomic ones can provide powerful opportunities for plant breeding through the identification of resistant biomarker metabolites which have the advantage of integrating the genetic background and the influence of the environment. In the past decade, several metabolomics attempts have been made to decipher the chemical defense that cereals employ to counteract F. graminearum. By covering the major classes of metabolites that have been highlighted and addressing their potential role, this review demonstrates the complex and integrated network of events that cereals can orchestrate to resist to F. graminearum.

Bioguided isolation, characterization, and biotransformation by Fusarium verticillioides of maize kernel compounds that inhibit fumonisin production.

Fusarium verticillioides infects maize ears, causing ear rot disease and contamination of grain with fumonisin mycotoxins. This contamination can be reduced by the presence of bioactive compounds in kernels that are able to inhibit fumonisin biosynthesis. To identify such compounds, we used kernels from a maize genotype with moderate susceptibility to F. verticillioides, harvested at the milk-dough stage (i.e., when fumonisin production initiates in planta), and applied a bioguided fractionation approach. Chlorogenic acid was the most abundant compound in the purified active fraction and its contribution to fumonisin inhibitory activity was up to 70%. Moreover, using a set of maize genotypes with different levels of susceptibility, chlorogenic acid was shown to be significantly higher in immature kernels of the moderately susceptible group. Altogether, our data indicate that chlorogenic acid may considerably contribute to either maize resistance to Fusarium ear rot, fumonisin accumulation, or both. We further investigated the mechanisms involved in the inhibition of fumonisin production by chlorogenic acid and one of its hydrolyzed products, caffeic acid, by following their metabolic fate in supplemented F. verticillioides broths. Our data indicate that F. verticillioides was able to biotransform these phenolic compounds and that the resulting products can contribute to their inhibitory activity.

Targeting of Antifungal Metabolites from Grapevine Byproducts by UPLC-HRMS/MS Approaches Using Bioactivity-Based Molecular Networking.

This study focuses on countering Fusarium graminearum, a harmful fungal pathogen impacting cereal crops and human health through mycotoxin production. These mycotoxins, categorized as type B trichothecenes, pose significant health risks. Research explores natural alternatives to synthetic fungicides, particularly investigating phenolics in grapevine byproducts. Thirteen eco-extracts from five French grape varieties (Merlot, Cabernet Sauvignon, Sauvignon blanc, Tannat, and Artaban) exhibited substantial antifungal properties, with ten extracts displaying remarkable effects. Extracts from grapevine stems and roots notably reduced fungal growth by over 91% after five days. Through UHPLC-HRMS/MS analysis and metabolomics, the study identified potent antifungal compounds such as ampelopsin A and cyphostemmin B, among other oligomeric stilbenes. Interestingly, this approach showed that flavan-3-ols have been identified as markers for extracts that induce fungal growth. Root extracts from rootstocks, rich in oligostilbenes, demonstrated the highest antifungal activity. This research underscores grapevine byproducts' potential both as a sustainable approach to control F. graminearum and mycotoxin contamination in cereal crops and the presence of different metabolites from the cultivars of grapevine, suggesting different activities.

Stilbenoids as Promising Natural Product-Based Solutions in a Race against Mycotoxigenic Fungi: A Comprehensive Review.

Exposure to mycotoxins can pose a variety of adverse health effects to mammals. Despite dozens of mycotoxin decontamination strategies applied from pre- to postharvest stages, it is always challenging to guarantee a safe level of these natural toxic compounds in food and feedstuffs. In the context of the increased occurrence of drug-resistance strains of mycotoxin-producing fungi driven by the overuse of fungicides, the search for new natural-product-based solutions is a top priority. This review aims to shed a light on the promising potential of stilbenoids extracted from renewable agricultural wastes (e.g., grape canes and forestry byproducts) as antimycotoxin agents. Deeper insights into the mode of actions underlying the bioactivity of stilbenoid molecules against fungal pathogens, together with their roles in plant defense responses, are provided. Safety aspects of these natural compounds on humans and ecology are discussed. Perspectives on the development of stilbenoid-based formulations using encapsulation technology, which allows the bypassing of the limitations related to stilbenoids, particularly low aqueous solubility, are addressed. Optimistically, the knowledge gathered in the present review supports the use of currently underrated agricultural byproducts to produce stilbenoid-abundant extracts with a high efficiency in the mitigation of mycotoxins in food and feedstuffs.

Carotenoids Occurring in Maize Affect the Redox Homeostasis of Fusarium graminearum and Its Production of Type B Trichothecene Mycotoxins: New Insights Supporting Their Role in Maize Resistance to Giberella Ear Rot.

Fusarium graminearum is the causal agent of Gibberella ear rot (GER) in maize, a devastating fungal disease resulting in yield reduction and contamination of grains with type B trichothecene (TCTB) mycotoxins. Reducing GER damage requires the implementation of an integrated management strategy in which the use of resistant maize genotypes is a key factor. The present study aimed at providing new phenotyping tools to improve breeding pipelines by investigating the yet understudied contribution of carotenoids to GER resistance. Here, we demonstrated for the first time the efficiency of carotenoid extracts from various maize genotypes to inhibit the production of TCTB by F. graminearum. We further suggested that zeaxanthin could be a key actor of this inhibition efficiency, notably via a negative transcriptional control of several biosynthetic genes of the TCTB pathway. Besides, we demonstrated that zeaxanthin treatments led to profound perturbations in the fungal redox homeostasis by affecting the expression of key genes encoding ROS detoxifying enzymes, several of them being involved in F. graminearum virulence during plant infection. Altogether, our data support the contribution of carotenoids to the mechanisms employed by maize to counteract F. graminearum infection and its production of TCTB.