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1. Fusarium graminearum Infection Strategy in Wheat Involves a Highly Conserved Genetic Program That Controls the Expression of a Core Effectome

Author

Florian Rocher, Tarek Alouane, Géraldine Philippe, Marie-Laure Martin, Philippe Label, Thierry Langin, Ludovic Bonhomme, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mathématiques et Informatique Appliquées (MIA Paris-Saclay), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Physique et Physiologie Intégratives de l’Arbre en environnement Fluctuant (PIAF), WheatOMICS, FEDER, ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), ANR-17-EURE-0007,SPS-GSR,Ecole Universitaire de Recherche de Sciences des Plantes de Paris-Saclay(2017), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)

Subjects
Fusarium graminearum, Triticum aestivum, plant–fungus interaction, in planta, transcriptomics, effectoromics, susceptibility factors, QH301-705.5, [SDV]Life Sciences [q-bio], Catalysis, Inorganic Chemistry, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, plant-fungus interaction, Spectroscopy, Organic Chemistry, food and beverages, General Medicine, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Computer Science Applications, Chemistry
Abstract

Fusarium graminearum, the main causal agent of Fusarium Head Blight (FHB), is one of the most damaging pathogens in wheat. Because of the complex organization of wheat resistance to FHB, this pathosystem represents a relevant model to elucidate the molecular mechanisms underlying plant susceptibility and to identify their main drivers, the pathogen’s effectors. Although the F. graminearum catalog of effectors has been well characterized at the genome scale, in planta studies are needed to confirm their effective accumulation in host tissues and to identify their role during the infection process. Taking advantage of the genetic variability from both species, a RNAseq-based profiling of gene expression was performed during an infection time course using an aggressive F. graminearum strain facing five wheat cultivars of contrasting susceptibility as well as using three strains of contrasting aggressiveness infecting a single susceptible host. Genes coding for secreted proteins and exhibiting significant expression changes along infection progress were selected to identify the effector gene candidates. During its interaction with the five wheat cultivars, 476 effector genes were expressed by the aggressive strain, among which 91% were found in all the infected hosts. Considering three different strains infecting a single susceptible host, 761 effector genes were identified, among which 90% were systematically expressed in the three strains. We revealed a robust F. graminearum core effectome of 357 genes expressed in all the hosts and by all the strains that exhibited conserved expression patterns over time. Several wheat compartments were predicted to be targeted by these putative effectors including apoplast, nucleus, chloroplast and mitochondria. Taken together, our results shed light on a highly conserved parasite strategy. They led to the identification of reliable key fungal genes putatively involved in wheat susceptibility to F. graminearum, and provided valuable information about their putative targets.

Published
2022
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2. Intestinal toxicity of the new type A trichothecenes, NX and 3ANX

Author

Sylvie Puel, J. David Miller, Laura Soler, Isabelle P. Oswald, Yannick Lippi, Manon Neves, Alix Pierron, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Carleton College, This research was supported in part by the ANR grant 'Newmyco' (ANR-15-CE21-0010), the ANR grant 'EmergingMyco' (ANR-18-CE34-0014) and the Ontario Ministry of Food and Agriculture (FS2015-2617/SF6115)., ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), ANR-18-CE34-0014,EmergingMyco,Les mycotoxines émergentes : un nouveau risque pour l'Homme et les animaux ?(2018), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)

Subjects
Fusarium, Environmental Engineering, Swine, Health, Toxicology and Mutagenesis, Cell, Explant, Trichothecenes, Type A, Transcriptome, 03 medical and health sciences, Immune system, medicine, Environmental Chemistry, Animals, Humans, Gut, Intestinal Mucosa, 030304 developmental biology, 0303 health sciences, biology, Cell growth, Chemistry, Gene Expression Profiling, 030302 biochemistry & molecular biology, Public Health, Environmental and Occupational Health, General Medicine, General Chemistry, biology.organism_classification, Pollution, Molecular biology, Deoxynivalenol, 3. Good health, Fusarium graminearum, medicine.anatomical_structure, Vacuolization, Apoptosis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Caco-2 Cells, Trichothecenes
Abstract

International audience; NX and its acetylated form 3ANX are two new type A trichothecenes produced by Fusarium graminearum whose toxicity is poorly documented. The aim of this study was to obtain a general view of the intestinal toxicity of these toxins. Deoxynivalenol (DON), which differs from NX by the keto group at C8, served as a benchmark. The viability of human intestinal Caco-2 cells decreased after 24 h of exposure to 3 μM NX (−21.4%), 3 μM DON (−20.2%) or 10 μM 3ANX (−17.4%). Histological observations of porcine jejunal explants exposed for 4 h to 10 μM of the different toxins showed interstitial edema and cellular debris. Explants exposed to NX also displayed cell vacuolization, a broken epithelial barrier and high loss of villi. Whole transcriptome profiling revealed that NX, DON and 3ANX modulated 369, 146 and 55 genes, respectively. Functional analyses indicated that the three toxins regulate the same gene networks and signaling pathways mainly; cell proliferation, differentiation, apoptosis and growth, and particularly immune and pro-inflammatory responses. Greater transcriptional impacts were observed with NX than with DON. In conclusion, our data revealed that the three toxins have similar impacts on the intestine but of different magnitude: NX > DON ≫ 3ANX. NX and 3ANX should consequently be included in overall risk analysis linked to the presence of trichothecenes in our diet.

Published
2022

3. Comparative Genomics of Eight Fusarium graminearum Strains with Contrasting Aggressiveness Reveals an Expanded Open Pangenome and Extended Effector Content Signatures

Author

Alouane, Tarek, Rimbert, Hélène, Bormann, Jörg, González-Montiel, Gisela A., Loesgen, Sandra, Schäfer, Wilhelm, Freitag, Michael, Langin, Thierry, Bonhomme, Ludovic, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Universität Hamburg (UHH), Oregon State University (OSU), Department of Chemistry, University of Florida, University of Florida [Gainesville] (UF), MCB1818006, CH1808717, ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)

Subjects
pangenome, QH301-705.5, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, Polymorphism, Single Nucleotide, Article, Fusarium, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Biology (General), secreted protein clusters, QD1-999, Triticum, Fusarium graminearum, Plant Diseases, Computational Biology, food and beverages, Genomics, aggressiveness, Biological Evolution, Chemistry, Fusarium head blight, Host-Pathogen Interactions, intra-species genomic diversity, proteinaceous effectors, Genome, Fungal
Abstract

Fusarium graminearum, the primary cause of Fusarium head blight (FHB) in small-grain cereals, demonstrates remarkably variable levels of aggressiveness in its host, producing different infection dynamics and contrasted symptom severity. While the secreted proteins, including effectors, are thought to be one of the essential components of aggressiveness, our knowledge of the intra-species genomic diversity of F. graminearum is still limited. In this work, we sequenced eight European F. graminearum strains of contrasting aggressiveness to characterize their respective genome structure, their gene content and to delineate their specificities. By combining the available sequences of 12 other F. graminearum strains, we outlined a reference pangenome that expands the repertoire of the known genes in the reference PH-1 genome by 32%, including nearly 21,000 non-redundant sequences and gathering a common base of 9250 conserved core-genes. More than 1000 genes with high non-synonymous mutation rates may be under diverse selection, especially regarding the trichothecene biosynthesis gene cluster. About 900 secreted protein clusters (SPCs) have been described. Mostly localized in the fast sub-genome of F. graminearum supposed to evolve rapidly to promote adaptation and rapid responses to the host’s infection, these SPCs gather a range of putative proteinaceous effectors systematically found in the core secretome, with the chloroplast and the plant nucleus as the main predicted targets in the host cell. This work describes new knowledge on the intra-species diversity in F. graminearum and emphasizes putative determinants of aggressiveness, providing a wealth of new candidate genes potentially involved in the Fusarium head blight disease.

Published
2021

4. Regulation of Secondary Metabolism in the Penicillium Genus

Author

Isabelle P. Oswald, Christelle El Hajj Assaf, Ali Atoui, Nadia Tahtah, Sophie Lorber, Olivier Puel, Chrystian Zetina-Serrano, André El Khoury, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Research Institute for Agricultural, Fisheries and Food (ILVO), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Saint-Joseph de Beyrouth (USJ), Faculty of Sciences [Lebanese University], Lebanese University [Beirut] (LU), International Cooperation Program CAPES/COFECUB (project number Sv 947/19), ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), and ANR-17-CE21-0008,PATRISK,REDUCTION DU RISQUE PATULINE GRACE A UNE GESTION INTEGREE ET DURABLE DE LA PRODUCTION DE POMME ET DE PRODUITS DERIVES(2017)

Subjects
0301 basic medicine, Ochratoxin A, animal structures, Range (biology), [SDV]Life Sciences [q-bio], 030106 microbiology, Biology, Catalysis, Inorganic Chemistry, Patulin, lcsh:Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Human health, Genus, transcription factors, Botany, control of gene expression, Physical and Theoretical Chemistry, Secondary metabolism, Mycotoxin, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, secondary metabolism, Organic Chemistry, Penicillium, food and beverages, regulation, General Medicine, 15. Life on land, biology.organism_classification, Computer Science Applications, virulence, 030104 developmental biology, chemistry, lcsh:Biology (General), lcsh:QD1-999, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Penicillium, one of the most common fungi occurring in a diverse range of habitats, has a worldwide distribution and a large economic impact on human health. Hundreds of the species belonging to this genus cause disastrous decay in food crops and are able to produce a varied range of secondary metabolites, from which we can distinguish harmful mycotoxins. Some Penicillium species are considered to be important producers of patulin and ochratoxin A, two well-known mycotoxins. The production of these mycotoxins and other secondary metabolites is controlled and regulated by different mechanisms. The aim of this review is to highlight the different levels of regulation of secondary metabolites in the Penicillium genus.

Published
2020

5. Searching for FHB Resistances in Bread Wheat: Susceptibility at the Crossroad

Author

Francis Fabre, Ludovic Bonhomme, Tarek Alouane, Florian Rocher, Thierry Langin, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Region Auvergne-Rhone-Alpes, ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)

Subjects
0106 biological sciences, 0301 basic medicine, Fusarium, Total resistance, Mini Review, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Triticum aestivum, Plant Science, lcsh:Plant culture, 01 natural sciences, 03 medical and health sciences, Head blight, lcsh:SB1-1110, 2. Zero hunger, Genetics, biology, Wheat diseases, S genes, New resistance sources, food and beverages, biology.organism_classification, Pathogenicity, Fusarium graminearum, 030104 developmental biology, fungal effectors, susceptibility factors, scab, 010606 plant biology & botany
Abstract

International audience; Fusarium head blight (FHB), primarily caused byFusarium graminearum, is one of the most devastating fungal wheat diseases. During the past decades, many efforts have been deployed to dissect FHB resistance, investigating both the wheat responses to infection and, more recently, the fungal determinants of pathogenicity. Although no total resistance has been identified so far, they demonstrated that some plant functions and the expression of specific genes are needed to promote FHB. Associated with the increasing list ofF. graminearumeffectors able to divert plant molecular processes, this fact strongly argues for a functional link between susceptibility-related factors and the fate of this disease in wheat. In this review, we gather more recent data concerning the involvement of plant and fungal genes and the functions and mechanisms in the development of FHB susceptibility, and we discuss the possibility to use them to diversify the current sources of FHB resistance.

Published
2020

6. From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites

Author

Isabelle P. Oswald, Emilien L. Jamin, Thaïs Hautbergue, Olivier Puel, Laurent Debrauwer, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, MetaboHUB, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), This study was co-funded by INRA and French Minister of Higher Education and Research in the context of a project supported by French National Agency of Research (ANR-15-CE21-0010-21Newmyco), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), OSWALD, Isabelle, Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques - - Newmyco2015 - ANR-15-CE21-0010 - AAPG2015 - VALID, and Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID

Subjects
Proteomics, 0301 basic medicine, MESH: Isotope Labeling, MESH: Genomics / methods, [SDV]Life Sciences [q-bio], Secondary Metabolism, Biochemistry, Gene Knockout Techniques, Drug Discovery, Data Mining, MESH: Gene Knockout Techniques, Animal health, Drug discovery, Culture environment, Genomics, MESH: Proteomics / methods, [SDV.TOX] Life Sciences [q-bio]/Toxicology, MESH: Secondary Metabolism, [SDV.TOX.TVM] Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Isotope Labeling, Multigene Family, MESH: Genome, Fungal, Identification (biology), Genome, Fungal, MESH: Metabolomics / methods, Emerging technologies, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Computational biology, Biology, 03 medical and health sciences, Metabolomics, MESH: Computer Simulation, MESH: Drug Discovery, Computer Simulation, MESH: Biological Products / metabolism, Secondary metabolism, MESH: Biological Products / isolation & purification, Biological Products, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, MESH: Fungi / metabolism, Organic Chemistry, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Fungi, MESH: Fungi / genetics, MESH: Data Mining / methods, 030104 developmental biology, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, MESH: Multigene Family
Abstract

International audience; Fungal secondary metabolites are defined by bioactive properties that ensure adaptation of the fungus to its environment. Although some of these natural products are promising sources of new lead compounds especially for the pharmaceutical industry, others pose risks to human and animal health. The identification of secondary metabolites is critical to assessing both the utility and risks of these compounds. Since fungi present biological specificities different from other microorganisms, this review covers the different strategies specifically used in fungal studies to perform this critical identification. Strategies focused on the direct detection of the secondary metabolites are firstly reported. Particularly, advances in high-throughput untargeted metabolomics have led to the generation of large datasets whose exploitation and interpretation generally require bioinformatics tools. Then, the genome-based methods used to study the entire fungal metabolic potential are reported. Transcriptomic and proteomic tools used in the discovery of fungal secondary metabolites are presented as links between genomic methods and metabolomic experiments. Finally, the influence of the culture environment on the synthesis of secondary metabolites by fungi is highlighted as a major factor to consider in research on fungal secondary metabolites. Through this review, we seek to emphasize that the discovery of natural products should integrate all of these valuable tools. Attention is also drawn to emerging technologies that will certainly revolutionize fungal research and to the use of computational tools that are necessary but whose results should be interpreted carefully.

Published
2018

7. Review article: Role of satiety hormones in anorexia induction by Trichothecene mycotoxins

Author

Marc Maresca, Isabelle P. Oswald, Chloé Terciolo, Philippe Pinton, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), ANR-15-CE21-0001,CaDON,Cadmium et Deoxynivalenol dans les récoltes de blé dur: comprendre les évènements de contamination croisée et évaluer la toxicité du mélange.(2015), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, OSWALD, Isabelle, Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques - - Newmyco2015 - ANR-15-CE21-0010 - AAPG2015 - VALID, and Cadmium et Deoxynivalenol dans les récoltes de blé dur: comprendre les évènements de contamination croisée et évaluer la toxicité du mélange. - - CaDON2015 - ANR-15-CE21-0001 - AAPG2015 - VALID

Subjects
0301 basic medicine, medicine.medical_specialty, Trichothecene, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Food Contamination, Enteroendocrine cell, Anorexia, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Toxicology, Satiety Response, 03 medical and health sciences, biology.animal, Internal medicine, medicine, Animals, Humans, Mink, Cholecystokinin, Gastrointestinal tract, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, digestive, oral, and skin physiology, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Medicine, Emesis, Deoxynivalenol, Gut hormones, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, 030104 developmental biology, Endocrinology, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.TOX.TVM] Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Hypothalamus, Peptide YY, [SDV.TOX]Life Sciences [q-bio]/Toxicology, medicine.symptom, Trichothecenes, hormones, hormone substitutes, and hormone antagonists, Food Science
Abstract

International audience; The trichothecenes, produced by Fusarium, contaminate animal feed and human food in all stages of production and lead to a large spectrum of adverse effects for animal and human health. An hallmark of trichothecenes toxicity is the onset of emesis followed by anorexia and food intake reduction in different animal species (mink, mice and pig). The modulation of emesis and anorexia can result from a direct action of trichothecenes in the brain or from an indirect action in the gastrointestinal tract. The direct action of trichothecenes involved specific brain areas such as nucleate tractus solitarius in the brainstem and the arcuate nuclei in the hypothalamus. Activation of these areas in the brain leads to the activation of specific neuronal populations containing anorexigenic factors (POMC and CART). The indirect action of trichothecenes in the gastrointestinal tract involved, by enteroendocrine cells, the secretion of several gut hormones such as cholecystokinin (CCK) and peptide YY (PYY) but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP) and 5-hydroxytryptamine (5-HT), which transmitted signals to the brain via the gut-brain axis. This review summarizes current knowledge on the effects of trichothecenes, especially deoxynivalenol, on emesis and anorexia and discusses the mechanisms underlying trichothecenes-induced food reduction.

Published
2018

8. Evidencing 98 secondary metabolites of Penicillium verrucosum using substrate isotopic labeling and high-resolution mass spectrometry

Author

Isabelle P. Oswald, Michel Pean, Olivier Puel, Thaïs Hautbergue, Emilien L. Jamin, Souria Tadrist, Marcel Delaforge, Lauriane Meneghetti, Laurent Debrauwer, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Axiom Platform, MetaToul-MetaboHUB, National Infrastructure of Metabolomics and Fluxomics, Groupe de Recherches Appliquées en Phytotechnologie (GRAP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Microbiologie Environnementale et Moléculaire (MEM), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), French National Infrastructureof Metabolomics and Fluxomics (MetaboHUB-ANR-11-INBS-0010), ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Puel, Olivier, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, penicillium verrucosum, [SDV]Life Sciences [q-bio], Clinical Biochemistry, mass spectrum analysis, toxicologie alimentaire, stable isotope labeling, Fungus, secondary metabolite, Secondary metabolite, Mass spectrometry, Biochemistry, Analytical Chemistry, Isotopic labeling, 03 medical and health sciences, Metabolomics, spectrométrie de masse, medicine, Penicillium verrucosum, Metabolome, Chromatography, High Pressure Liquid, mass spectrometry, molecular networking, Chromatography, biology, Chemistry, public health, fungus, Penicillium, Cell Biology, General Medicine, biology.organism_classification, 030104 developmental biology, métabolite secondaire, santé publique, Isotope Labeling, secondary plant products, medicine.drug
Abstract

Industrial applications of fungal compounds, coupled with the emergence of fungal threats to natural ecosystems and public health, have increased interest in filamentous fungi. Among all pathogenic fungi, Penicillium verrucosum is one of the most common mold-infecting stored cereals in temperate regions. However, it is estimated that 80% of fungal secondary metabolites remain unknown. To detect new P. verrucosum compounds, an untargeted metabolomic approach was applied to fungus grown on wheat grains labeled with stable isotopes: (i) natural grains (99% 12C); (ii) grains enriched with 97% of 13C; and (iii) grains enriched with 53% of 13C and 97% of 15N. Analyses performed by high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) enabled the specific detection of fungal metabolites, and the unambiguous characterization of their chemical formulas. In this way, 98 secondary metabolites were detected and their chemical formulas were determined. Of these, only 18 identifications could be made based on databases, the literature and mass spectrometry fragmentation experiments, with the result that 80 were totally unknown. Molecular networks were generated to analyze these results, leading to the characterization by MSn experiments of a new fungisporin produced by P. verrucosum. More generally, this article provides precise mass spectrometric data about all these compounds for further studies of the Penicillium metabolome.

Published
2017

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