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1. Monitoring red wine maturation in oak barrels using 1H NMR-based metabolomics

Author

Inès Le Mao, Grégory Da Costa, Guillaume Leleu, and Tristan Richard

Subjects
Wine ageing, 1H NMR, targeted analysis, fingerprinting, Agriculture, Botany, QK1-989
Abstract

Wine maturation in oak barrels is a well-known winemaking practice that, among other things, brings roundness and complexity to wine. Studying wine evolution during barrel maturation is crucial to ensure wine quality. Red wines produced in a wine growing estate of the Bordeaux region were monitored after one and twelve months of maturation in oak barrels in the estate’s cellar. Wines were kept in oak casks from three different manufacturers. The evolution of the wine constituents during maturation was monitored by 1H NMR-based metabolomics combined with multivariate statistical analysis. NMR spectra were submitted to targeted and untargeted approaches. The wine maturation effects were thereby monitored and the discriminant metabolites identified. The wines analysed after one month of maturation exhibit higher contents of amino acids, catechin and epicatechin, acetoin and choline than the wines analysed twelve months after maturation; for their part, the latter wines showed higher contents of acetic acid, ethyl lactate, arabinose and glucose. In addition, significant differences were observed between the wines depending on the barrel manufacturers.

Published
2024

2. Endo metabolomic profiling of flor and wine yeasts reveals a positive correlation between intracellular metabolite load and the specific glycolytic flux during wine fermentation

Author

Charlotte Vion, Mathilde Brambati, Grégory Da Costa, Tristan Richard, and Philippe Marullo

Subjects
phenotypic trade-offs, flor and wine yeast, metabolite load, 1H-NMR, fermentation kinetics, Microbiology, QR1-502
Abstract

This study explored the intracellular metabolic variations between 17 strains of Saccharomyces cerevisiae belonging to two different genetic populations: flor and wine yeasts, in the context of alcoholic fermentation. These two populations are closely related as they share the same ecological niche but display distinct genetic characteristics. A protocol was developed for intracellular metabolites extraction and 1H-NMR analysis. This methodology allowed us to identify and quantify 21 intracellular metabolites at two different fermentation steps: the exponential and stationary phases. This work provided evidence of significant differences in the abundance of intracellular metabolites, which are strain- and time-dependent, thus revealing complex interactions. Moreover, the differences in abundance appeared to be correlated with life-history traits such as average cell size and specific glycolytic flux, which revealed unsuspected phenotypic correlations between metabolite load and fermentation activity.

Published
2023
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3. 1H-NMR metabolomics for wine screening and analysis

Author

Inès Le Mao, Grégory Da Costa, and Tristan Richard

Subjects
Wine, 1H-NMR, Metabolomics, Authenticity, Winemaking, targeted, Agriculture, Botany, QK1-989
Abstract

The number of metabolomic studies has grown steadily over the last twenty years. Among the fields of application, food sciences are broadly represented. Proton NMR (1H-NMR) is a commonly used technique for metabolomics and is particularly suitable for wine analysis, because the major wine constituents are highly dependent on biotic and abiotic conditions. 1H-NMR-based metabolomics were used first to guarantee the authenticity of wines, and more recently to determine the impact of viticultural or oenological practices using both targeted and untargeted protocols. This state-of-the-art review covers the different analytical methodologies developed to ensure wine traceability from sample preparation to 1H-NMR spectrum analysis. The potential applications of 1H-NMR spectroscopy in oenology, from wine authenticity control to the monitoring of winemaking, are described. The challenges and perspectives of the deployment of NMR for oenological monitoring are also discussed.

Published
2023
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4. Chemical process to improve natural grapevine-cane extract effectivity against powdery mildew and grey mould

Author

Tristan Richard, Toni El Khawand, David Taillis, Grégory Da Costa, Eric Pedrot, Stéphanie Cluzet, Alain Decendit, and Josep Valls Fonayet

Subjects
resveratrol, viniferin, grapevine, oxidative coupling, Plasmopara viticola, Botrytis cinerea, Agriculture, Botany, QK1-989
Abstract

Grapevine canes are vine growing byproducts studied for their antimicrobial activities. These properties are directly connected to the stilbene content; oligomeric stilbenes being the most active. In this study, we propose a chemical process, based on oxidative coupling, using metals to increase the oligostilbene rate and the biological effectivity of cane extract against grapevine pathogens. A total of ten compounds were obtained and identified by combining LCMS and NMR spectroscopies, including four newly reported compounds: trans-oxistilbenin C, trans-oxistilbenin D, and cis- and trans-oxistilbenin E. The extract and the main stilbene formed were evaluated for their preventive effects on Plasmopara viticola and Botrytis cinerea growth. The processed extract was highly effective against both pathogens.

Published
2021
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5. Enterobacteriaceae are essential for the modulation of colitis severity by fungi

Author

Bruno Sovran, Julien Planchais, Sarah Jegou, Marjolene Straube, Bruno Lamas, Jane Mea Natividad, Allison Agus, Louise Dupraz, Jérémy Glodt, Grégory Da Costa, Marie-Laure Michel, Philippe Langella, Mathias L. Richard, and Harry Sokol

Subjects
Enterobacteriaceae, S. boulardii CNCM I-745, C. albicans, Colitis, Microbiota, Fungi, Microbial ecology, QR100-130
Abstract

Abstract Background Host-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD). Here we focused on bacteria-fungi interactions and their implications on intestinal inflammation, a poorly understood area. Methods Dextran sodium sulfate (DSS)-induced colitis was assessed in mice treated with vancomycin (targeting gram-positive bacteria) or colistin (targeting Enterobacteriaceae) and supplemented with either Saccharomyces boulardii CNCM I-745 or Candida albicans. Inflammation severity as well as bacterial and fungal microbiota compositions was monitored. Results While S. boulardii improved DSS-induced colitis and C. albicans worsened it in untreated settings, antibiotic treatment strongly modified DSS susceptibility and effects of fungi on colitis. Vancomycin-treated mice were fully protected from colitis, while colistin-treated mice retained colitis phenotype but were not affected anymore by administration of fungi. Antibacterial treatments not only influenced bacterial populations but also had indirect effects on fungal microbiota. Correlations between bacterial and fungal relative abundance were dramatically decreased in colistin-treated mice compared to vancomycin-treated and control mice, suggesting that colistin-sensitive bacteria are involved in interactions with fungi. Restoration of the Enterobacteriaceae population by administrating colistin-resistant Escherichia coli reestablished both beneficial effects of S. boulardii and pathogenic effects of C. albicans on colitis severity. This effect was at least partly mediated by an improved gut colonization by fungi. Conclusions Fungal colonization of the gut is affected by the Enterobacteriaceae population, indirectly modifying effects of mycobiome on the host. This finding provides new insights into the role of inter-kingdom functional interactions in intestinal physiopathology and potentially in IBD.

Published
2018
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6. Unusual stilbene glucosides from Vitis vinifera roots

Author

Tristan Richard, Iris Aja, Grégory Da Costa, Eric Pedrot, Marie-Laure Iglesias, Antonio Palos Pinto, Josep Valls, Nassima Chaher, M. Begoña Ruiz-Larrea, Jean-Michel Mérillon, Djebbar Atmani, and José Ignacio Ruiz Sanz

Subjects
antiproliferative effects, cytotoxicity, HepG2 cells, phytoalexins, resveratrol, stilbene glucosides, Agriculture, Botany, QK1-989
Abstract

Aim: Stilbenes are well-known phytoalexins present in vine and wine. Stilbene glucosides have been identified in wine; however, other than piceid, these compounds have never been reported to be present in the woody parts of grapevine. The aims of this study were to investigate the presence of stilbene glucosides in the woody parts of the vine and to evaluate their cytotoxic activity, in comparison with that of resveratrol, in human hepatoma HepG2 cells. Methods and results: Stilbene glucosides were isolated from a Vitis vinifera root extract. The extract was partitioned with ethyl acetate and fractionated by polyamide gel column chromatography. Pure compounds were obtained by semipreparative high-performance liquid chromatography. These were then identified by mass spectrometry and nuclear magnetic resonance (NMR) analyses, including analysis of two-dimensional NMR spectra. In addition to resveratrol, five stilbene glucosides were found: resveratroloside, resveratrol rutinoside, trans-ε-viniferin diglucoside, cis-ε-viniferin diglucoside and piceid. Of these, the first four showed cytotoxic effects against HepG2 cells when the crystal violet assay was used to determine cell viability. Conclusion: In addition to resveratrol and piceid, this is the first report of the presence of four glucosylated derivatives of resveratrol (resveratroloside, resveratrol rutinoside, and trans- and cis-ε-viniferin diglucosides) in the woody parts of vine. These compounds showed significant cytotoxicity against HepG2 cells. Significance and impact of the study: Stilbenes are well-known biological compounds. Grapevine is one of the main sources of this family of polyphenols. Other than piceid, stilbene glucosides have been identified in wine but never in the woody parts of vine. This is the first study in which five glucosylated derivatives of resveratrol were isolated from woody parts of vine. They were also shown to exert antiproliferative effects in human hepatoma HepG2 cells.

Published
2019
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7. Rbt1 protein domains analysis in Candida albicans brings insights into hyphal surface modifications and Rbt1 potential role during adhesion and biofilm formation.

Author

Céline Monniot, Anita Boisramé, Grégory Da Costa, Muriel Chauvel, Marc Sautour, Marie-Elisabeth Bougnoux, Marie-Noëlle Bellon-Fontaine, Frédéric Dalle, Christophe d'Enfert, and Mathias L Richard

Subjects
Medicine, Science
Abstract

Cell wall proteins are central to the virulence of Candida albicans. Hwp1, Hwp2 and Rbt1 form a family of hypha-associated cell surface proteins. Hwp1 and Hwp2 have been involved in adhesion and other virulence traits but Rbt1 is still poorly characterized. To assess the role of Rbt1 in the interaction of C. albicans with biotic and abiotic surfaces independently of its morphological state, heterologous expression and promoter swap strategies were applied. The N-terminal domain with features typical of the Flo11 superfamily was found to be essential for adhesiveness to polystyrene through an increase in cell surface hydrophobicity. A 42 amino acid-long domain localized in the central part of the protein was shown to enhance the aggregation function. We demonstrated that a VTTGVVVVT motif within the 42 amino acid domain displayed a high β-aggregation potential and was responsible for cell-to-cell interactions by promoting the aggregation of hyphae. Finally, we showed through constitutive expression that while Rbt1 was directly accessible to antibodies in hyphae, it was not so in yeast. Similar results were obtained for another cell wall protein, namely Iff8, and suggested that modification of the cell wall structure between yeast and hyphae can regulate the extracellular accessibility of cell wall proteins independently of gene regulation.

Published
2013
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8. 1H-NMR Metabolomics as a Tool for Winemaking Monitoring

Author

Soizic Lacampagne, Tristan Richard, Charlyne Bautista, Inès Le Mao, Jean Martin-Pernier, Grégory Da Costa, Unité de Recherche Oenologie [Villenave d'Ornon], and Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SDV]Life Sciences [q-bio], Metabolite, Pharmaceutical Science, Organic chemistry, 01 natural sciences, Article, Analytical Chemistry, chemistry.chemical_compound, 0404 agricultural biotechnology, Metabolomics, QD241-441, Drug Discovery, Food science, Physical and Theoretical Chemistry, wine, 1 H-NMR, Winemaking, 2. Zero hunger, Wine, Chemistry, Pea protein, 010401 analytical chemistry, 1H-NMR, food and beverages, 04 agricultural and veterinary sciences, 040401 food science, metabolomics, winemaking, 0104 chemical sciences, Multiple factors, Chemistry (miscellaneous), Proton NMR, Molecular Medicine, Viticulture
Abstract

The chemical composition of wine is known to be influenced by multiple factors including some viticulture practices and winemaking processes. 1H-NMR metabolomics has been successfully applied to the study of wine authenticity. In the present study, 1H-NMR metabolomics in combination with multivariate analysis was applied to investigate the effects of grape maturity and enzyme and fining treatments on Cabernet Sauvignon wines. A total of forty wine metabolites were quantified. Three different stages of maturity were studied (under-maturity, maturity and over-maturity). Enzyme treatments were carried out using two pectolytic enzymes (E1 and E2). Finally, two proteinaceous fining treatments were compared (vegetable protein, fining F1, pea protein and PVPP, fining F2). The results show a clear difference between the three stages of maturity, with an impact on different classes of metabolites including amino acids, organic acids, sugars, phenolic compounds, alcohols and esters. A clear separation between enzymes E1 and E2 was observed. Both fining agents had a significant effect on metabolite concentrations. The results demonstrate that 1H-NMR metabolomics provides a fast and robust approach to study the effect of winemaking processes on wine metabolites. These results support the interest to pursue the development of 1H-NMR metabolomics to investigate the effects of winemaking on wine quality.

Published
2021

9. Gut microbiota-derived short-chain fatty acids regulate IL-17 production by mouse and human intestinal γδ T cells

Author

Marie-Laure Michel, Allison Agus, Madeleine Spatz, Mathias L. Richard, Philippe Langella, Chloé Michaudel, Camille Danne, Sothea Touch, Julien Planchais, Grégory Da Costa, Harry Sokol, François Trottein, Aurélie Magniez, Nathalie Rolhion, Camille Mayeur, Louise Dupraz, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Paris Center for Microbiome Medicine, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), L.D. is supported by the Foundation for Medical Research. This work is supported, in part, by the Association Francois Aupetit., Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5

Subjects
Male, Antibiotics, Gut flora, Inflammatory bowel disease, Mice, 0302 clinical medicine, Intestinal inflammation, Cecum, chemistry.chemical_classification, 0303 health sciences, Interleukin-17, Receptors, Antigen, T-Cell, gamma-delta, Middle Aged, 3. Good health, γδ, Intestines, IL-17, Histone, 030220 oncology & carcinogenesis, gut, Female, Interleukin 17, Adult, medicine.drug_class, T cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, digestive system, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Vancomycin, medicine, Animals, Humans, propionate, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Interleukins, Fatty Acids, Volatile, Inflammatory Bowel Diseases, biology.organism_classification, medicine.disease, SCFA, Gastrointestinal Microbiome, Gastrointestinal Tract, Histone Deacetylase Inhibitors, Mice, Inbred C57BL, chemistry, Immunology, Propionate, biology.protein
Abstract

International audience; Gut interleukin-17A (IL-17)-producing γδ T cells are tissue-resident cells that are involved in both host defense and regulation of intestinal inflammation. However, factors that regulate their functions are poorly understood. In this study, we find that the gut microbiota represses IL-17 production by cecal γδ T cells. Treatment with vancomycin, a Gram-positive bacterium-targeting antibiotic, leads to decreased production of short-chain fatty acids (SCFAs) by the gut microbiota. Our data reveal that these microbiota-derived metabolites, particularly propionate, reduce IL-17 and IL-22 production by intestinal γδ T cells. Propionate acts directly on γδ T cells to inhibit their production of IL-17 in a histone deacetylase-dependent manner. Moreover, the production of IL-17 by human IL-17-producing γδ T cells from patients with inflammatory bowel disease (IBD) is regulated by propionate. These data contribute to a better understanding of the mechanisms regulating gut γδ T cell functions and offer therapeutic perspectives of these cells.

Published
2021

10. Chemical process to improve natural grapevine-cane extract effectivity against powdery mildew and grey mould

Author

David Taillis, Eric Pedrot, Grégory Da Costa, Tristan Richard, Alain Decendit, Toni El Khawand, Josep Valls Fonayet, Stéphanie Cluzet, Unité de Recherche Oenologie [Villenave d'Ornon], Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011)

Subjects
0106 biological sciences, Horticulture, resveratrol, 01 natural sciences, oxidative coupling, lcsh:Agriculture, Plasmopara viticola, Botrytis cinerea, lcsh:Botany, Cane, viniferin, biology, Chemistry, 010401 analytical chemistry, lcsh:S, food and beverages, biology.organism_classification, Antimicrobial, 0104 chemical sciences, grapevine, lcsh:QK1-989, [SDE]Environmental Sciences, Powdery mildew, 010606 plant biology & botany, Food Science
Abstract

International audience; Grapevine canes are vine growing byproducts studied for their antimicrobial activities. These properties are directly connected to the stilbene content; oligomeric stilbenes being the most active. In this study, we propose a chemical process, based on oxidative coupling, using metals to increase the oligostilbene rate and the biological effectivity of cane extract against grapevine pathogens. A total of ten compounds were obtained and identified by combining LCMS and NMR spectroscopies, including four newly reported compounds: trans-oxistilbenin C, trans-oxistilbenin D, and cis- and trans-oxistilbenin E. The extract and the main stilbene formed were evaluated for their preventive effects on Plasmopara viticola and Botrytis cinerea growth. The processed extract was highly effective against both pathogens.

Published
2021

11. Enterobacteriaceae are essential for the modulation of colitis severity by fungi

Author

Julien Planchais, Mathias L. Richard, Marie-Laure Michel, Bruno Lamas, Louise Dupraz, Sarah Jegou, Allison Agus, Grégory Da Costa, Harry Sokol, Marjolène Straube, Philippe Langella, Jane M. Natividad, Bruno Sovran, Jérémy Glodt, AgroParisTech, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, HAL UPMC, Gestionnaire, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Richard, Mathias, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Microbiology (medical), medicine.drug_class, [SDV]Life Sciences [q-bio], Antibiotics, Population, Microbiology, Antibodies, lcsh:Microbial ecology, enterobacteriaceae, S. boulardii CNCM I-745, C. albicans, colitis, microbiota, fungi, Mice, 03 medical and health sciences, 0302 clinical medicine, Enterobacteriaceae, Antibiosis, Candida albicans, medicine, Animals, Humans, Colitis, education, 2. Zero hunger, education.field_of_study, biology, Research, Microbiota, Fungi, biology.organism_classification, medicine.disease, Corpus albicans, Gastrointestinal Microbiome, 3. Good health, Mice, Inbred C57BL, Saccharomyces boulardii, [SDV] Life Sciences [q-bio], Disease Models, Animal, 030104 developmental biology, Vancomycin, lcsh:QR100-130, Female, 030211 gastroenterology & hepatology, medicine.drug
Abstract

Background Host-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD). Here we focused on bacteria-fungi interactions and their implications on intestinal inflammation, a poorly understood area. Methods Dextran sodium sulfate (DSS)-induced colitis was assessed in mice treated with vancomycin (targeting gram-positive bacteria) or colistin (targeting Enterobacteriaceae) and supplemented with either Saccharomyces boulardii CNCM I-745 or Candida albicans. Inflammation severity as well as bacterial and fungal microbiota compositions was monitored. Results While S. boulardii improved DSS-induced colitis and C. albicans worsened it in untreated settings, antibiotic treatment strongly modified DSS susceptibility and effects of fungi on colitis. Vancomycin-treated mice were fully protected from colitis, while colistin-treated mice retained colitis phenotype but were not affected anymore by administration of fungi. Antibacterial treatments not only influenced bacterial populations but also had indirect effects on fungal microbiota. Correlations between bacterial and fungal relative abundance were dramatically decreased in colistin-treated mice compared to vancomycin-treated and control mice, suggesting that colistin-sensitive bacteria are involved in interactions with fungi. Restoration of the Enterobacteriaceae population by administrating colistin-resistant Escherichia coli reestablished both beneficial effects of S. boulardii and pathogenic effects of C. albicans on colitis severity. This effect was at least partly mediated by an improved gut colonization by fungi. Conclusions Fungal colonization of the gut is affected by the Enterobacteriaceae population, indirectly modifying effects of mycobiome on the host. This finding provides new insights into the role of inter-kingdom functional interactions in intestinal physiopathology and potentially in IBD. Electronic supplementary material The online version of this article (10.1186/s40168-018-0538-9) contains supplementary material, which is available to authorized users.

Published
2018

12. Unusual stilbene glucosides from Vitis vinifera roots

Author

Marie-Laure Iglesias, Iris Aja, José Ignacio Ruiz Sanz, Eric Pedrot, Tristan Richard, Djebbar Atmani, Antonio Palos Pinto, Jean-Michel Mérillon, Josep Valls, Nassima Chaher, Grégory Da Costa, M. Begoña Ruiz-Larrea, University of the Basque Country, Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), and Université Abderrahmane Mira [Béjaïa]

Subjects
phytoalexins, Ethyl acetate, Horticulture, Resveratrol, resveratrol, lcsh:Agriculture, chemistry.chemical_compound, Column chromatography, Resveratroloside, lcsh:Botany, [SDV.IDA]Life Sciences [q-bio]/Food engineering, antiproliferative effects, cytotoxicity, HepG2 cells, stilbene glucosides, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Cytotoxicity, Piceid, Wine, Chromatography, lcsh:S, food and beverages, lcsh:QK1-989, chemistry, Polyphenol, Food Science
Abstract

International audience; Aim: Stilbenes are well-known phytoalexins present in vine and wine. Stilbene glucosides have been identified in wine; however, other than piceid, these compounds have never been reported to be present in the woody parts of grapevine. The aims of this study were to investigate the presence of stilbene glucosides in the woody parts of the vine and to evaluate their cytotoxic activity, in comparison with that of resveratrol, in human hepatoma HepG2 cells. Methods and results: Stilbene glucosides were isolated from a Vitis vinifera root extract. The extract was partitioned with ethyl acetate and fractionated by polyamide gel column chromatography. Pure compounds were obtained by semipreparative high-performance liquid chromatography. These were then identified by mass spectrometry and nuclear magnetic resonance (NMR) analyses, including analysis of two-dimensional NMR spectra. In addition to resveratrol, five stilbene glucosides were found: resveratroloside, resveratrol rutinoside, trans-epsilon-viniferin diglucoside, cis-epsilon-viniferin diglucoside and piceid. Of these, the first four showed cytotoxic effects against HepG2 cells when the crystal violet assay was used to determine cell viability. Conclusion: In addition to resveratrol and piceid, this is the first report of the presence of four glucosylated derivatives of resveratrol (resveratroloside, resveratrol rutinoside, and trans- and cis-epsilon-viniferin diglucosides) in the woody parts of vine. These compounds showed significant cytotoxicity against HepG2 cells. Significance and impact of the study: Stilbenes are well-known biological compounds. Grapevine is one of the main sources of this family of polyphenols. Other than piceid, stilbene glucosides have been identified in wine but never in the woody parts of vine. This is the first study in which five glucosylated derivatives of resveratrol were isolated from woody parts of vine. They were also shown to exert antiproliferative effects in human hepatoma HepG2 cells.

Published
2019

13. Impact of polyphenols on receptor-ligand interactions by NMR the case of neurotensin (NT)-neurotensin receptor fragment (NTS1) complex

Author

Stéphane Quideau, Arnaud Bondon, Tahiri Sylla, Grégory Da Costa, Jean-Pierre Monti, Jean-Michel Mérillon, Eva Petit, Tristan Richard, Laurent Pouységu, Unité de Recherche Oenologie [Villenave d'Ornon], Institut des Sciences de la Vigne et du Vin (ISVV)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Physiologie Pathologie et Génétique Végétales (PPGV), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique et biophysique, Université Bordeaux Segalen - Bordeaux 2, Institut des Sciences Chimiques de Rennes (ISCR), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), ANR-11-INBS-0010, Bordeaux Metabolome Facility, and MetaboHUB, Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Unité de Recherche Oenologie [Villenave d'Ornon] (OENO), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie, Pathologie et Génétique Végétales (PPGV), Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011)

Subjects
Models, Molecular, 030303 biophysics, interaction, phenolic compounds, Receptor-ligand complex, Ligands, 03 medical and health sciences, chemistry.chemical_compound, Structural Biology, Receptors, Neurotensin, [CHIM]Chemical Sciences, neurodegenerative diseases, Neurotensin receptor, Receptor, receptor–ligand complex, Molecular Biology, Neurotensin, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, fungi, food and beverages, Polyphenols, General Medicine, Ligand (biochemistry), NMR, 3. Good health, Biochemistry, chemistry, Polyphenol
Abstract

International audience; Ligand-receptor interactions can be implicated in many pathological events such as chronic neurodegenerative diseases. Thus, the discovery of molecules disrupting this type of interactions could be an interesting therapeutic approach. Polyphenols are well known for their affinity for proteins and several studies have characterized these direct interactions. But studying the direct influence of multi-therapeutic drugs on a ligand-receptor complex relevant to a neurodegenerative disorder is a challenging issue. Solution NMR, molecular modeling and iterative calculations were used to obtain information about the interaction between a phenolic compound, α-glucogallin (α-2) and a ligand/fragment receptor complex neurotensin (NT) and its receptor NTS1. The α-2 was shown to bind to NT and a peptidic fragment of its NTS1 receptor, independently. Although the formation of the corresponding ligand-receptor complex did not seem to be affected, this experimental modeling protocol will enable the evaluation of other anti-amyloidogenic compounds such as blockers of NT-NTS1 binding. These types of studies help in understanding the specificity and influence in binding and can provide information to develop new molecules with a putative pharmacological interest.

Published
2019

14. Impact of different elicitors on grapevine leaf metabolism monitored by 1H NMR spectroscopy

Author

Aleksandra Burdziej, Louis Gougeon, Anthony Bellée, Anna Szakiel, Stéphanie Cluzet, Inès Le Mao, Tristan Richard, Jean-Michel Mérillon, Grégory Da Costa, Marie-France Corio-Costet, Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), University of Warsaw (UW), Santé et agroécologie du vignoble (UMR SAVE), and Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)

Subjects
Endocrinology, Diabetes and Metabolism, Metabolite, Proton Magnetic Resonance Spectroscopy, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Cyclopentanes, 01 natural sciences, Biochemistry, MeJA, 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, ASM, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Plant defense against herbivory, Vitis, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Oxylipins, Nuclear magnetic resonance spectroscopy, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Principal Component Analysis, Methyl jasmonate, Jasmonic acid, 010401 analytical chemistry, food and beverages, 0104 chemical sciences, Elicitor, Plant Leaves, Metabolic pathway, chemistry, Vitis vinifera, [SDE]Environmental Sciences, Metabolomic analysis, Phosphonates, Salicylic Acid, Salicylic acid
Abstract

International audience; INTRODUCTION: Grapevine protection is an important issue in viticulture. To reduce pesticide use, sustainable disease control strategies are proposed, including a promising alternative method based on the elicitor-triggered stimulation of the grapevine natural defense responses. However, detailed investigations are necessary to characterize the impact of such defense induction on the primary metabolism. OBJECTIVES: Our aim was to use a metabolomics approach to assess the impact on grapevine of different elicitors dependent on the salicylic acid (SA) and/or jasmonic acid (JA) pathway. For this purpose, leaves of grapevine foliar cuttings were treated with methyl jasmonate, acibenzolar-S-methyl or phosphonates. METHODS: According to the elicitor, common and discriminating metabolites were elucidated using 1H NMR measurements and principal component analysis. RESULTS: A wide range of compounds including carbohydrates, amino acids, organic acids, phenolics and amines were identified. The score plots obtained by combining PC1 versus PC2 and PC1 versus PC3 allowed a clear separation of samples, so metabolite fingerprinting showed an extensive reprogramming of primary metabolic pathways after elicitation. CONCLUSION: The methods applied were found to be accurate for the rapid determination and differential characterization of plant samples based on their metabolic composition. These investigations can be very useful because the application of plant defense stimulators is gaining greater importance as an alternative strategy to pesticides in the vineyard.

Published
2019

15. H-1 NMR metabolomics applied to Bordeaux red wines

Author

François Guyon, Tristan Richard, Grégory Da Costa, Louis Gougeon, Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), and Service Commun des Laboratoires

Subjects
Vintage, Wine, bordeaux wines, multivariate statistics, 010401 analytical chemistry, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, 01 natural sciences, Vineyard, 0104 chemical sciences, Analytical Chemistry, Horticulture, 0404 agricultural biotechnology, Geography, q-NMR, Statistical analyses, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Wine classification, red wines, wine classification, Food Science
Abstract

International audience; The q-NMR metabolomics has already demonstrated its potential for classifying wines of different geographical origins, grape varieties, or vintages. This study focuses on the characterisation of Bordeaux red wines, seeking to discriminate them from others produced in the major French wine regions. A sampling of 224 commercial French wines was analysed by 1H NMR and forty compounds were quantified. Non-supervised and supervised statistical analyses revealed a singular imprint of Bordeaux wines in comparison with other French wines, with classification rates ranging from 71% to 100%. Within the Bordeaux vineyards, red wines from the different Bordeaux subdivisions were analysed from different vintages. Our results indicate that q-NMR metabolomics enables the differentiation of Médoc and Libournais vineyard highlighting the most discriminant constituents. In addition, the effects of wine evolution during bottle aging and vintage on Bordeaux red wines were pointed out and discussed.

Published
2019

16. Wine authenticity by quantitative 1H NMR versus multitechnique analysis: a case study

Author

Louis Gougeon, Tristan Richard, François Guyon, Grégory Da Costa, Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), and Service Commun des Laboratoires

Subjects
Vintage, Alternative methods, Wine, Computer science, business.industry, 010401 analytical chemistry, Pattern recognition, 04 agricultural and veterinary sciences, 040401 food science, 01 natural sciences, Applied Microbiology and Biotechnology, Data treatment, 0104 chemical sciences, Analytical Chemistry, Counterfeit, Comparative evaluation, Low volume, 0404 agricultural biotechnology, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Artificial intelligence, Safety, Risk, Reliability and Quality, business, Safety Research, Food Science
Abstract

International audience; Food counterfeit is a major issue for food industries. In the case of wines, there can be multiple forgeries such as geographical, vintage, or varietal mislabeling. For the last 10 years, the use of quantitative 1H NMR (q-NMR) for food authentication has experienced an enormous increase. This study was based on a comparative evaluation of the results obtained for three sets of authentic high-valued wines and suspected wines. Two methodologies have been followed: (i) the usual wine analysis, based on the utilization of multiple techniques, which is the traditional way of analysis for wine authentication and (ii) q-NMR profiling, the alternative proposed method. For wine comparison, an original approach based on similarity score (S-score) by analogy to the Z-score calculation was developed. A limit of four S-scores outside the range − 2/2 has been, arbitrary, defined to reveal that wines are different using q-NMR analysis. Data treatments allowed the extraction of discriminating parameters, some of which were common to both approaches while others could be linked to the techniques’ capabilities showing the complementarity of the two approaches. This study demonstrated the potential of q-NMR in wine authentication by comparative analysis with authentic samples. The q-NMR alternative method has also the advantages of rapidity (around 20 min including sample preparation, analysis, and data treatment) and low volume (0.5 mL), which is a prerequisite for analyzing priceless wines.

Published
2019

17. Identification of bioactive compounds from Fraxinus angustifolia extracts with anti- NADH oxidase activity of bovine milk xanthine oxidoreductase

Author

Nassima Chaher, Djebbar Atmani, Grégory Da Costa, Nadjia Ahmane, Meriem Rahmani-Berboucha, Karima Ayouni, Tristan Richard, Dina Atmani-Kilani, Nadjet Debbache-Benaida, Unité de Recherche Oenologie [Villenave d'Ornon], and Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Physiology, phenolics, 0206 medical engineering, hyperuricemia, 02 engineering and technology, Fraxinus angustifolia, Biology, Microbiology, Article, xanthine oxidoreductase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucoside, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Molecular Biology, chemistry.chemical_classification, Oxidase test, Reactive oxygen species, Superoxide, Cell Biology, biology.organism_classification, 020601 biomedical engineering, Fraxinus angustifolia,NADH oxidase,xanthine oxidoreductase,phenolics,hyperuricemia, 3. Good health, Enzyme, chemistry, Biochemistry, NADH oxidase, 030220 oncology & carcinogenesis, visual_art, visual_art.visual_art_medium, Bark, General Agricultural and Biological Sciences, Kaempferol
Abstract

Fraxinus angustifolia leaves and bark are used in traditional medicine against various inflammatory-related pathologies incumbent to reactive oxygen species (ROS) generation by the NADH oxidase activity of enzymes such as xanthine oxidoreductase (XOR). This study was designed to investigate the in vitro and in vivo inhibitory activities of this enzyme by Fraxinus angustifolia extracts. The leaf organic phase of ethyl acetate (LFA) and its bark aqueous counterpart (BFA) showed the strongest anti-NADH oxidase activity in vitro (IC50 = 38.51 and 42.04 μg mL-1, respectively). They consequently suppressed superoxide generation both enzymatically (53% and 19%, respectively) and nonenzymatically (34% and 19%, respectively). These results were corroborated in vivo, with high anti- NADH oxidase potential of the leaves and bark extracts (75.32% and 51.32%, respectively) concomitant with moderate hypouricemic activities (36.84% and 38.59%, respectively). Bio-guided fractionation led to the identification, by LC-DAD-MS/MS, of esculin and calcelarioside in bark and kaempferol glucoside in leaves as the main compounds responsible for the anti-NADH oxidase activity of XOR. These results plead in favor of the use of F. angustifolia as a source of potentially interesting therapeutic substances.

Published
2019

18. Cyberlindnera jadinii and Kluyveromyces lactis, two fungi used in food processes, have potential probiotic effects on gut inflammation

Author

Cindy Hugot, Maxime Poirier, Madeleine Spatz, Gregory Da Costa, Chloé Michaudel, Alexia Lapiere, Camille Danne, Valérie Martin, Philippe Langella, Harry Sokol, Marie-Laure Michel, Patrick Boyaval, and Mathias L. Richard

Subjects
yeasts, gut microbiota, inflammatory bowel disease, Microbiology, QR1-502
Abstract

ABSTRACT Many strains have been used and selected by the food industry for their capacities to ferment, produce flavors, or produce heterologous molecules. Very little is known about the diversity of foodborne yeasts and their potential effect on gut microbiota and gut health. We initiated a complete characterization of five strains belonging to five species with a long history of safe use in food: Cyberlindnera jadinii, Debaryomyces hansenii, Kazachstania unispora, Kluyveromyces lactis, and Pichia membranifaciens, with a focus on their capacity to protect against gut inflammation using an in vivo dextran sodium sulfate-induced colitis model in mice. C. jadinii and K. lactis living cells showed a clear reduction in mouse sensitivity to colitis in vivo. Interestingly, we observed that C. jadinii had the capacity to survive transit in the gut, while K. lactis did not. We demonstrated that C. jadinii was unable to efficiently adhere to epithelial cells and did not survive more than 24 to 48 h in the gut. Transcriptomic analysis using NanoString technology suggested a potential role of IL-8 through Mif and Fkbp5 in the effect of C. jadinii on the immune system. Bacterial and fungal microbiota characterization showed a modification of both microbiota after C. jadinii treatment, with a significant increase in positive microorganisms and a decrease in pathobionts. Altogether, these data suggest that both C. jadinii and K. lactis strains have potential as probiotic yeast strains to fight against inflammation in the gut, but further studies are needed to understand the mechanisms by which these strains act on gut health.IMPORTANCEThe food industry has always used many strains of microorganisms including fungi in their production processes. These strains have been widely characterized for their biotechnological value, but we still know very little about their interaction capacities with the host at a time when the intestinal microbiota is at the center of many pathologies. In this study, we characterized five yeast strains from food production which allowed us to identify two new strains with high probiotic potential and beneficial effects in a model of intestinal inflammation.

Published
2023
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19. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice

Author

Mathias L. Richard, Philippe Langella, Patrick Veiga, Marie Laure Michel, Julien Planchais, Grégory Da Costa, Harry Sokol, Bruno Sovran, Celia Chamignon, Jane M. Natividad, Johan E. T. van Hylckama Vlieg, Dominique Rainteau, Chantal Bridonneau, Bruno Lamas, Hang-Phuong Pham, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Danone Nutricia Research [Palaiseau, France], Centre Daniel Carasso [Palaiseau, France], Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), This work was supported by a grant in aid from Danone Nutricia Research., Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Sokol , Harry, Gestionnaire, Hal Sorbonne Université, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Blood Glucose, Male, 0301 basic medicine, General Physics and Astronomy, Gut flora, Mice, 0302 clinical medicine, Liver Function Tests, lcsh:Science, bile-acids, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Metabolic Syndrome, Multidisciplinary, biology, Lacticaseibacillus rhamnosus, food and beverages, induced obesity, dysbiosis, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Desulfovibrionaceae Infections, Liver, 030220 oncology & carcinogenesis, Cytokines, medicine.symptom, expression data, Metabolic Networks and Pathways, Akkermansia muciniphila, medicine.medical_specialty, Science, Inflammation, Bilophila, Diet, High-Fat, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Lactobacillus rhamnosus, Internal medicine, medicine, Animals, bacteremia, gut microbiota, akkermansia-muciniphila, intestinal barrier, inflammation, butyrate, business.industry, Probiotics, General Chemistry, medicine.disease, biology.organism_classification, Dietary Fats, Gastrointestinal Microbiome, Fatty Liver, Mice, Inbred C57BL, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Bilophila wadsworthia, 030104 developmental biology, Endocrinology, lcsh:Q, Steatosis, Metabolic syndrome, Transcriptome, business, Dysbiosis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis reveal pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation demonstrate the bacterium’s intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Administration of the probiotic Lactobacillus rhamnosus CNCM I-3690 limits B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results suggest a new avenue for interventions against western diet-driven inflammatory and metabolic diseases., Lipid intake is known to promote Bilophila wadsworthia growth. Here the authors show that B. wadsworthia aggravates high fat diet induced metabolic dysfunctions and its suppression, both pharmacologically or mediated by Lactobacillus rhamnosus, limits the severity of metabolic impairment.

Published
2018

20. In vitro effects of serotonin, melatonin, and other related indole compounds on amyloid-β kinetics and neuroprotection

Author

Grégory Da Costa, Ana B. Cerezo, Ruth Hornedo-Ortega, M. Carmen Garcia-Parrilla, Ana M. Troncoso, Tristan Richard, Universidad de Sevilla, Unité de Recherche Oenologie [Villenave d'Ornon], and Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)

Subjects
0301 basic medicine, Tryptamine, Serotonin, Indoles, Magnetic Resonance Spectroscopy, indolic, vitagene system, Neuroprotection, PC12 Cells, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sirtuin 2, Microscopy, Electron, Transmission, Sirtuin 1, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Maladie d'Alzheimer, Tryptophol, Animals, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, MTT assay, HSP70 Heat-Shock Proteins, Senile plaques, Viability assay, Melatonin, Amyloid beta-Peptides, fibril formation, Chemistry, Circular Dichroism, Tryptophan, Peptide Amyloïde, amyloid-beta, Peptide Fragments, 3. Good health, Rats, Heme oxygenase, 030104 developmental biology, Neuroprotective Agents, Biochemistry, Gene Expression Regulation, Électrophorèse, 030217 neurology & neurosurgery, Heme Oxygenase-1, Food Science, Biotechnology
Abstract

International audience; Scope: Amyloid-beta peptide is the main component of senile plaques in Alzheimer's disease. The inhibition of amyloid-beta peptide assembly, the destabilization of amyloid-beta peptide aggregates, and the decrease of its cytotoxicity for the prevention of neuronal death are considered neuroprotective effects. In this work, the protective effects against amyloid-beta peptide aggregation and cytotoxicity of eight indolic compounds are evaluated: tryptophan, tryptamine, serotonin, tryptophol, N-acetylserotonin, 3-indoleacetic acid, tryptophan ethyl ester, and melatonin. Methods and results: Thioflavin T spectroscopic assay, transmission electron microscopy, western blotting, circular dichroism, NMR, cell viability (thiazolyl blue tetrazolium bromide assay), quantitative PCR, and heme oxygenase activity are used. Serotonin is the most effective compound for inhibiting amyloid-beta peptide aggregation. Almost all the indolic compounds tested prevent amyloid-beta peptide-induced and increase cell viability, being between 9 and 25%. Melatonin and serotonin are the most active. Moreover, serotonin increased the expression of SIRT-1 and 2, heat shock protein 70, and heme oxygenase activity, this being a possible mechanism underlying the observed neuroprotective effect. Conclusion: Melatonin and other related indolic compounds, mainly serotonin, show an inhibitory and destabilizing effect on amyloid-beta peptide fibril formation and they possess neuroprotective properties related to the vitagenes system.

Published
2018

21. Wine analysis and authenticity using 1H-NMR metabolomics data: application to chinese wines

Author

Grégory Da Costa, Tristan Richard, Wen Ma, François Guyon, Pierre-Louis Teissedre, Louis Gougeon, Inès Le Mao, Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), and Service Commun des Laboratoires

Subjects
Oenologie, wine composition, 01 natural sciences, Applied Microbiology and Biotechnology, Analytical Chemistry, 0404 agricultural biotechnology, Metabolomics, authenticity, wine analysis, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Food science, Safety, Risk, Reliability and Quality, Chine, Winemaking, Terroir, Wine, Chemistry, 010401 analytical chemistry, Cabernet Sauvignon, food and beverages, 04 agricultural and veterinary sciences, 040401 food science, qNMR, 0104 chemical sciences, Metabolomics data, traceability, Composé phénolique, Vin, Proton NMR, NMR-based metabolomics, Cultivar, Multivariate statistical, Safety Research, Food Science
Abstract

International audience; A NMR-based metabolomics method was developed to semiautomatically quantify the main components of wine. The method was applied to discriminate wines from two regions of China, Shanxi and Ningxia, which were produced by 6 wineries and for 6 vintages. Two different cultivars, Cabernet Sauvignon and Beihong, were used for winemaking. The method allowed the quantification of 33 metabolites including sugars, amino acids, organic acids, alcohols, and phenolic compounds. Depending on the compounds, the LOD values were in the range of 0.6 to 116 mg/L. The results showed that NMR-based metabolomics combined with multivariate statistical analysis allowed wine separation as a function of terroir and cultivar. Nevertheless, wine differentiation as a function of wineries and ageing would need to be examined more carefully.

Published
2018

22. Mucosa-associated microbiota dysbiosis in colitis associated cancer

Author

Giuseppina Liguori, Massimo Pierluigi Di Simone, Carlo Calabrese, Philippe Langella, Thomas W. Hoffmann, Massimo Campieri, Giovanni Brandi, Gilberto Poggioli, Mathias L. Richard, Bruno Lamas, Grégory Da Costa, Harry Sokol, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Departement Hopital Universitaire, Partenaires INRAE, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), 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-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Xeda International S.A, Richard, Ml, Liguori, G, Lamas, B, Brandi, G, da Costa, G, Hoffmann, Tw, Di Simone MP, Calabrese, C, Poggioli, G, Langella, P, Campieri, M, and Sokol, H.

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Gut flora, Inflammatory bowel disease, Cohort Studies, Intestinal mucosa, Crohn Disease, RNA, Ribosomal, 16S, mucosa-associated microbiota, Intestinal Mucosa, Cancer, Aged, 80 and over, biology, Gastroenterology, Biodiversity, dysbiosis, Middle Aged, Colitis, 3. Good health, Infectious Diseases, Female, Colorectal Neoplasms, fungal microbiota, Microbiology (medical), Adult, Microbiology, digestive system, 03 medical and health sciences, DNA, Ribosomal Spacer, medicine, Humans, Aged, Bacteria, Ruminococcus, dysbiosi, Fungi, biology.organism_classification, medicine.disease, Inflammatory Bowel Diseases, Gastrointestinal Microbiome, stomatognathic diseases, 030104 developmental biology, Fusobacterium, Immunology, Research Paper/Report, Colitis, Ulcerative, Dysbiosis
Abstract

International audience; Gut microbiota dysbiosis has been associated with inflammatory bowel diseases (IBD). In colorectal cancer, the gut microbiota has also been recognized as potentially involved in aggravating or favoring the tumor development. However, very little is known on the structure and role of the microbiota in colitis associated cancer (CAC), an important complication of IBD in human. Here we analyzed the bacterial and fungal composition of the mucosa associated microbiota of patients suffering CAC, sporadic cancer (SC) and of healthy subjects (HS) by barcode sequences analysis on the following cohort: 7 CAC patients, 10 SC patients and 10 HS using 16S (MiSeq) and ITS2 (pyrosequencing) sequencing, for bacteria and fungi respectively. Mucosa-associated bacterial microbiota in CAC was significantly different from the ones in SC or in HS, while the fungal showed no differences. Comparison between mucosa-associated microbiota on the tumor site or in normal mucosa near the tumor showed very similar patterns. The global mucosa-associated bacterial microbiota in cancer patients was characterized by a restriction in biodiversity but no change for the fungal community. Compared to SC, CAC was characterized by an increase of Enterobacteriacae family and Sphingomonas genus and a decrease of Fusobacterium and Ruminococcus genus. Our study confirms the alteration of the mucosa-associated bacterial microbiota in IBD and SC. Although the cohort is limited in number, this is the first evidence of the existence of an altered bacterial microbiota in CAC clearly different from the one in SC patients.

Published
2018

23. Antibiotic treatment using amoxicillin-clavulanic acid impairs gut mycobiota development through modification of the bacterial ecosystem

Author

Madeleine Spatz, Gregory Da Costa, Rebecka Ventin-Holmberg, Julien Planchais, Chloé Michaudel, Yazhou Wang, Camille Danne, Alexia Lapiere, Marie-Laure Michel, Kaija-Leena Kolho, Philippe Langella, Harry Sokol, and Mathias L. Richard

Subjects
Microbiota, Mycobiota, Antibiotics, Enterobacteriaceae, Microbial ecology, QR100-130
Abstract

Abstract Background Effects of antibiotics on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the fungal microbiota (mycobiota). It is commonly believed that fungal load increases in the gastrointestinal tract following antibiotic treatment, but better characterization is clearly needed of how antibiotics directly or indirectly affect the mycobiota and thus the entire microbiota. Design We used samples from humans (infant cohort) and mice (conventional and human microbiota-associated mice) to study the consequences of antibiotic treatment (amoxicillin-clavulanic acid) on the intestinal microbiota. Bacterial and fungal communities were subjected to qPCR or 16S and ITS2 amplicon-based sequencing for microbiota analysis. In vitro assays further characterized bacterial-fungal interactions, with mixed cultures between specific bacteria and fungi. Results Amoxicillin-clavulanic acid treatment triggered a decrease in the total fungal population in mouse feces, while other antibiotics had opposite effects on the fungal load. This decrease is accompanied by a total remodelling of the fungal population with the enrichment in Aspergillus, Cladosporium, and Valsa genera. In the presence of amoxicillin-clavulanic acid, microbiota analysis showed a remodeling of bacterial microbiota with an increase in specific bacteria belonging to the Enterobacteriaceae. Using in vitro assays, we isolated different Enterobacteriaceae species and explored their effect on different fungal strains. We showed that Enterobacter hormaechei was able to reduce the fungal population in vitro and in vivo through yet unknown mechanisms. Conclusions Bacteria and fungi have strong interactions within the microbiota; hence, the perturbation initiated by an antibiotic treatment targeting the bacterial community can have complex consequences and can induce opposite alterations of the mycobiota. Interestingly, amoxicillin-clavulanic acid treatment has a deleterious effect on the fungal community, which may have been partially due to the overgrowth of specific bacterial strains with inhibiting or competing effects on fungi. This study provides new insights into the interactions between fungi and bacteria of the intestinal microbiota and might offer new strategies to modulate gut microbiota equilibrium. Video Abstract

Published
2023
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24. Saccharomyces boulardii CNCM I-745 supplementation during and after antibiotic treatment positively influences the bacterial gut microbiota

Author

Madeleine Spatz, Yazhou Wang, Alexia Lapiere, Gregory Da Costa, Chloé Michaudel, Camille Danne, Marie-Laure Michel, Philippe Langella, Harry Sokol, and Mathias L. Richard

Subjects
microbiota, mycobiota, antibiotics, Saccharomyces boulardii CNCM I-745, treatment, Medicine (General), R5-920
Abstract

IntroductionAntibiotic effects on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the mycobiota, the fungal part of the microbiota and how the length of administration influences both microbiota. Here, we examined the effect of antibiotics (ATB) on the composition of bacterial and fungal microbiota and how the administration of Saccharomyces boulardii CNCM I-745 influences both microbiota.MethodsIn order to get closer to the human microbiota, the mice used in this study were subjected to fecal microbiota transfer (FMT) using human feces and subsequently called human microbiotaassociated (HMA) mice. These mice were then treated with amoxicillinclavulanate antibiotics and supplemented with S. boulardii during and after ATB treatment to understand the effect of the yeast probiotic on both bacterial and fungal microbiota. Bacterial and fungal microbiota analyses were done using 16S and ITS2 rRNA amplicon-based sequencing.ResultsWe showed that the administration of S. boulardii during ATB treatment had very limited effect on the fungal populations on the long term, once the yeast probiotic has been cleared from the gut. Concerning bacterial microbiota, S. boulardii administration allowed a better recovery of bacterial populations after the end of the ATB treatment period. Additionally, 16S and ITS2 rRNA sequence analysis revealed that 7 additional days of S. boulardii administration (17 days in total) enhanced the return of the initial bacterial equilibrium.DiscussionIn this study, we provide a comprehensive analysis of how probiotic yeast administration can influence the fungal and bacterial microbiota in a model of broad-spectrum antibiotherapy.

Published
2023
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25. Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence

Author

Grégory Da Costa, Julien Planchais, Bruno Sovran, Mathias L. Richard, Chantal Bridonneau, Adrien Six, Philippe Langella, Bruno Lamas, Jane M. Natividad, Marie-Laure Michel, Myriam Delacre, Harry Sokol, Hang-Phuong Pham, Vassiliki Zacharioudaki, Nadine Waldschmitt, Louise Dupraz, Mathias Chamaillard, Microorganismes, Molécules Bioactives et Physiopathologie Intestinale (LBM-E4), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ANR ANR-13-BSV3-0014-01, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP]

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Diet therapy, IBD, Virulence, germfree mice, Colonisation resistance, Adaptive Immunity, Gut flora, pathogen-specific antibody, digestive system, Microbiology, Mice, 03 medical and health sciences, 0302 clinical medicine, fluids and secretions, Polysaccharides, Immunity, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Citrobacter rodentium, microbiota, Animals, Genetic Predisposition to Disease, Innate immune system, biology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Colitis, biology.organism_classification, Acquired immune system, Immunity, Innate, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Gastrointestinal Microbiome, 3. Good health, CARD Signaling Adaptor Proteins, stomatognathic diseases, 030104 developmental biology, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Gene-Environment Interaction, mono-and polysaccharides, Diet Therapy
Abstract

ObjectiveIn association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 (CARD9), a key innate immunity gene, is required to shape a normal gut microbiota. Card9–/– mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli. Here, we examined how CARD9 controls C. rodentium infection susceptibility through microbiota-dependent and microbiota-independent mechanisms.DesignC. rodentium infection was assessed in conventional and germ-free (GF) wild-type (WT) and Card9–/– mice. To explore the impact of Card9–/–microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or Card9–/– (Card9–/–→GF) microbiota before C. rodentium infection. Microbiota composition was determined by 16S rDNA gene sequencing. Inflammation severity was determined by histology score and lipocalin level. Microbiota–host immune system interactions were assessed by quantitative PCR analysis.ResultsCARD9 controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to C. rodentium-induced colitis was observed in Card9–/–→GF mice. The microbiota of Card9–/– mice failed to outcompete the monosaccharide-consuming C. rodentium, worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of C. rodentium and the defective pathogen-specific antibody response in Card9–/– mice.ConclusionsCARD9 modulates the susceptibility to intestinal infection by controlling the pathogen virulence in a microbiota-dependent and microbiota-independent manner. Genetic susceptibility to intestinal pathogens can be overridden by diet intervention that restores humoural immunity and a competing microbiota.

Published
2017

26. Staphylococcus epidermidis isolates from atopic or healthy skin have opposite effect on skin cells: potential implication of the AHR pathway modulation

Author

Leslie Landemaine, Gregory Da Costa, Elsa Fissier, Carine Francis, Stanislas Morand, Jonathan Verbeke, Marie-Laure Michel, Romain Briandet, Harry Sokol, Audrey Gueniche, Dominique Bernard, Jean-Marc Chatel, Luc Aguilar, Philippe Langella, Cecile Clavaud, and Mathias L. Richard

Subjects
S. epidermidis, aryl hydrocarbon receptor, indoles, inflammation, biofilms, proteases, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionStaphylococcus epidermidis is a commensal bacterium ubiquitously present on human skin. This species is considered as a key member of the healthy skin microbiota, involved in the defense against pathogens, modulating the immune system, and involved in wound repair. Simultaneously, S. epidermidis is the second cause of nosocomial infections and an overgrowth of S. epidermidis has been described in skin disorders such as atopic dermatitis. Diverse isolates of S. epidermidis co-exist on the skin. Elucidating the genetic and phenotypic specificities of these species in skin health and disease is key to better understand their role in various skin conditions. Additionally, the exact mechanisms by which commensals interact with host cells is partially understood. We hypothesized that S. epidermidis isolates identified from different skin origins could play distinct roles on skin differentiation and that these effects could be mediated by the aryl hydrocarbon receptor (AhR) pathway.MethodsFor this purpose, a library of 12 strains originated from healthy skin (non-hyperseborrheic (NH) and hyperseborrheic (H) skin types) and disease skin (atopic (AD) skin type) was characterized at the genomic and phenotypic levels.Results and discussionHere we showed that strains from atopic lesional skin alter the epidermis structure of a 3D reconstructed skin model whereas strains from NH healthy skin do not. All strains from NH healthy skin induced AhR/OVOL1 path and produced high quantities of indole metabolites in co-culture with NHEK; especially indole-3-aldehyde (IAld) and indole-3-lactic acid (ILA); while AD strains did not induce AhR/OVOL1 path but its inhibitor STAT6 and produced the lowest levels of indoles as compared to the other strains. As a consequence, strains from AD skin altered the differentiation markers FLG and DSG1. The results presented here, on a library of 12 strains, showed that S. epidermidis originated from NH healthy skin and atopic skin have opposite effects on the epidermal cohesion and structure and that these differences could be linked to their capacity to produce metabolites, which in turn could activate AHR pathway. Our results on a specific library of strains provide new insights into how S. epidermidis may interact with the skin to promote health or disease.

Published
2023
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27. Phenolic contents and bioactive potential of peach fruit extracts

Author

Arnaud Monvoisin, Hamza Temsamani, Stéphanie Cluzet, Tristan Richard, Stéphanie Krisa, Abderrahmane Mokrani, Jean-Michel Mérillon, Khodir Madani, Elodie Renouf, Grégory Da Costa, Marc Mesnil, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biomathématiques, Biophysique, Biochimie, et Scientométrie (L3BS), Université Abderrahmane Mira [Béjaïa], Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), CBMN-IPB, Université de Bordeaux (UB), USC 1366 Oenologie, Institut National de la Recherche Agronomique (INRA), Modulation Artificielle des Genes Eucaryotes, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Institut des Sciences de la Vigne et du Vin (ISVV)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Antioxidant, DPPH, medicine.medical_treatment, [SDV]Life Sciences [q-bio], PC12 Cells, Antioxidants, Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Prunus, 0404 agricultural biotechnology, Phenols, medicine, Animals, MTT assay, Food science, Isorhamnetin, ComputingMilieux_MISCELLANEOUS, Prunus persica, 030109 nutrition & dietetics, ABTS, 04 agricultural and veterinary sciences, General Medicine, Fluoresceins, 040401 food science, Rats, Biochemistry, chemistry, Polyphenol, Fruit, Composition (visual arts), Reactive Oxygen Species, Food Science, Chromatography, Liquid
Abstract

Several cultivars of peach fruit (Prunus persica L.) were investigated. Their phenolic composition and concentration were assessed by LC-MS. Concentrations were calculated in mg per g of dry weight extract. Their antioxidant capacity (Folin-Ciocalteu, ORAC, DPPH, ABTS, PFRAP and ICA), inhibitory property against β-amyloid and α-synuclein fibril formation and protective capacity against Aβ-induced toxicity on PC12 cell lines (viability assessed by MTT assay and intracellular ROS production by DCFH-DA assay) were evaluated. Fifteen different phenolic compounds were identified and quantified. In particular, new isorhamnetin derivatives were identified. Phenolic contents were ranged between 19 and 82mg/g. Spring Belle extract had the highest content and Romea the lowest. Except for the ICA assay, a good correlation between phenolic content and the antioxidant capacities of peach fruit extracts was found, indicating that phenolic compounds are major contributors to their antioxidant capacity. Results indicate that the phenolic extract of peach cultivars inhibits Aβ and αS fibril formation and protects PC12 cell lines against Aβ-induced toxicity.

Published
2016

28. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands

Author

Anne Bourrier, Jane M. Natividad, Soraya Taleb, Loic Brot, Chantal Bridonneau, Philippe Seksik, Laurent Beaugerie, Jacques Cosnes, Harry Sokol, Isabelle Nion-Larmurier, Marie-Laure Michel, Bernhard Ryffel, Jean-Marie Launay, Fatiha Merabtene, Hang-Phuong Pham, Ramnik J. Xavier, Sarah Jegou, Aurélie Couturier-Maillard, Philippe Langella, Bruno Lamas, Grégory Da Costa, Thomas W. Hoffmann, Valentin Leducq, Mathias L. Richard, Université Pierre et Marie Curie - Paris 6 (UPMC), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), McMaster Univ, Farncombe Family Digest Hlth Res Inst, Hamilton, ON L8S 4L8, Canada, Université Paris Diderot - Paris 7 (UPD7), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Technicolor [Cesson Sévigné], Technicolor, Equipe ATIP-Avenir, INSERM-ITMO SP, ECCO grant, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [APHP], Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP]

Subjects
Male, 0301 basic medicine, Gut flora, Inflammatory bowel disease, Mice, RNA, Ribosomal, 16S, Lactobacillus, Chromatography, High Pressure Liquid, Mice, Knockout, biology, Reverse Transcriptase Polymerase Chain Reaction, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Dextran Sulfate, Tryptophan, Interleukin, General Medicine, Fecal Microbiota Transplantation, Middle Aged, Colitis, 3. Good health, Cytokines, Female, Adult, Adolescent, Colon, digestive system, General Biochemistry, Genetics and Molecular Biology, Microbiology, Young Adult, 03 medical and health sciences, Immune system, inflammatory bowel disease, mucosal immunology, medicine, Animals, Humans, Gene Expression Profiling, Interleukins, Inflammatory Bowel Diseases, biology.organism_classification, medicine.disease, Aryl hydrocarbon receptor, Gastrointestinal Microbiome, CARD Signaling Adaptor Proteins, 030104 developmental biology, Receptors, Aryl Hydrocarbon, Mucosal immunology, Immunology, biology.protein
Abstract

International audience; Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9-/- mice are more susceptible to colitis. The microbiota is altered in Card9-/- mice, and transfer of the microbiota from Card9-/- to wild-type, germ-free recipients increases their susceptibility to colitis. The microbiota from Card9-/- mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation.

Published
2016

29. Hyphenating centrifugal partition chromatography with nuclear magnetic resonance through automated solid phase extraction

Author

Grégory Da Costa, Jonathan Bisson, Marion Brunel, Jean-Michel Mérillon, Alain Badoc, Pierre Waffo-Teguo, Tristan Richard, Groupe d’Etudes des Substances Végétales à Activité Biologique (GESVAB ), Unité de Recherche Oenologie [Villenave d'Ornon], and Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)

Subjects
Coupling, Chromatography, Centrifugal partition chromatography, Chemistry, Countercurrent exchange, 010401 analytical chemistry, 010402 general chemistry, 01 natural sciences, High-performance liquid chromatography, 0104 chemical sciences, Analytical Chemistry, Nuclear magnetic resonance, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Solid phase extraction, Two-dimensional nuclear magnetic resonance spectroscopy
Abstract

International audience; Centrifugal partition chromatography (CPC) and all countercurrent separation apparatus provide chemists with efficient ways to work with complex matrixes, especially in the domain of natural products. However, despite the great advances provided by these techniques, more efficient ways of analyzing the output flow would bring further enhancement. This study describe a hyphenated approach made by coupling NMR with CPC through a hybrid-indirect coupling made possible by using a solid phase extraction (SPE) apparatus intended for high-pressure liquid chromatography (HPLC)-NMR hyphenation. Some hardware changes were needed to adapt the incompatible flow-rates and a reverse-engineering approach that led to the specific software required to control the apparatus. 1D 1HNMR and 1H–1H correlation spectroscopy (COSY) spectra were acquired in reasonable time without the need for any solvent-suppression method thanks to the SPE nitrogen drying step. The reduced usage of expensive deuterated solvents from several hundreds of milliliters to the milliliter order is the major improvement of this approach compared to the previously published ones.

Published
2016

30. Deletion of both Dectin-1 and Dectin-2 affects the bacterial but not fungal gut microbiota and susceptibility to colitis in mice

Author

Yazhou Wang, Madeleine Spatz, Gregory Da Costa, Chloé Michaudel, Alexia Lapiere, Camille Danne, Allison Agus, Marie-Laure Michel, Mihai G. Netea, Philippe Langella, Harry Sokol, and Mathias L. Richard

Subjects
Microbiota, Gut inflammation, Dectin-1, Dectin-2, Immune response, Microbial ecology, QR100-130
Abstract

Abstract Background Innate immunity genes have been reported to affect susceptibility to inflammatory bowel diseases (IBDs) and colitis in mice. Dectin-1, a receptor for fungal cell wall β-glucans, has been clearly implicated in gut microbiota modulation and modification of the susceptibility to gut inflammation. Here, we explored the role of Dectin-1 and Dectin-2 (another receptor for fungal cell wall molecules) deficiency in intestinal inflammation. Design Susceptibility to dextran sodium sulfate (DSS)-induced colitis was assessed in wild-type, Dectin-1 knockout (KO), Dectin-2KO, and double Dectin-1KO and Dectin-2KO (D-1/2KO) mice. Inflammation severity, as well as bacterial and fungal microbiota compositions, was monitored. Results While deletion of Dectin-1 or Dectin-2 did not have a strong effect on DSS-induced colitis, double deletion of Dectin-1 and Dectin-2 significantly protected the mice from colitis. The protection was largely mediated by the gut microbiota, as demonstrated by fecal transfer experiments. Treatment of D-1/2KO mice with opportunistic fungal pathogens or antifungal agents did not affect the protection against gut inflammation, suggesting that the fungal microbiota had no role in the protective phenotype. Amplicon-based microbiota analysis of the fecal bacterial and fungal microbiota of D-1/2KO mice confirmed the absence of changes in the mycobiota but strong modification of the bacterial microbiota. We showed that bacteria from the Lachnospiraceae family were at least partly involved in this protection and that treatment with Blautia hansenii was enough to recapitulate the protection. Conclusions Deletion of both the Dectin-1 and Dectin-2 receptors triggered a global shift in the microbial gut environment, affecting, surprisingly, mainly the bacterial population and driving protective effects in colitis. Members of the Lachnospiraceae family seem to play a central role in this protection. These findings provide new insights into the role of the Dectin receptors, which have been described to date as affecting only the fungal population, in intestinal physiopathology and in IBD. Video Abstract

Published
2022
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31. Development of an analytical methodology using Fourier transform mass spectrometry to discover new structural analogs of wine natural sweeteners

Author

Axel Marchal, Jean-Michel Mérillon, Grégory Da Costa, Alice Bibès, Pierre Waffo-Teguo, Denis Dubourdieu, Eric Génin, Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), Thermo Fisher Scientific Inc., and Institut des Sciences de la Vigne et du Vin (ISVV)

Subjects
Oak wood, Liquid chromatography, Wine, Orbitrap, Mass spectrometry, Biochemistry, High resolution mass spectrometry, Fourier transform ion cyclotron resonance, Mass Spectrometry, Analytical Chemistry, law.invention, chemistry.chemical_compound, Quercus, Isomerism, Computational chemistry, law, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Drug Discovery, Environmental Chemistry, Organic chemistry, Targeted screening, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Spectroscopy, Chromatography, High Pressure Liquid, Biological Products, Fourier Analysis, Sweetness, Wood, Triterpenes, chemistry, Sweetening Agents, Derivative (chemistry)
Abstract

International audience; Volatile and non-volatile molecules are directly responsible for the thrill and excitement provided by wine-tasting. Their elucidation requires powerful analytical techniques and innovative methodologies. In a recent work, two novel sweet compounds called quercotriterpenosides (QTT) were identified in oak wood used for wine-ageing. The aim of the present study is to discover structural analogs of such natural sweeteners in oak wood. For this purpose, an analytical approach was developed as an alternative to chemical synthesis. Orbitrap mass spectrometry proved to be a crucial technique both to demonstrate the presence of QTT analogs in oak wood by targeted screening and to guide the purification pathway of these molecules using complementary chromatographic tools. Four compounds were isolated and identified for the first time: two isomers, one glucosyl derivative and one galloyl derivative of QTT. Their tasting showed that only the two new isomers were sweet, thus demonstrating both the pertinence of the strategy and the influence of functional groups on gustatory properties. Finally, this paper presents some developments involving multistage Fourier transform mass spectrometry (FTMS) to provide solid structural information on these functional groups prior to any purification of compounds. Such analytical developments could be particularly useful for research on taste-active or bio-active products.

Published
2015

32. Rbt1 Protein Domains Analysis in Candida albicans Brings Insights into Hyphal Surface Modifications and Rbt1 Potential Role during Adhesion and Biofilm Formation

Author

Marie-Noëlle Bellon-Fontaine, Anita Boisrame, Marc Sautour, Grégory Da Costa, Marie-Elisabeth Bougnoux, Mathias L. Richard, Frédéric Dalle, Céline Monniot, Christophe d'Enfert, Muriel Chauvel, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Biologie et Pathogénicité fongiques, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Sorbonne Paris Cité (USPC), Unité de Parasitologie-Mycologie, Service de Microbiologie [Hôpital Necker-Enfants-Malades, Paris], Assistance Publique - Hôpitaux de Paris, European Commission [FinSysB PITN-GA-2008-214004], Agence Nationale de la Recherche (KANJI) [ANR-08-MIE-033-01], French Government's Investissement d'Avenir program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' [ANR-10-LABX-62-IBEID], French Ministry of Research, ANR-10-LABX-0062/10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 214004, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), L. Richard, Mathias, Biologie et Pathogénicité fongiques (BPF), and Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)

Subjects
[SDV]Life Sciences [q-bio], lcsh:Medicine, biofilm, Cell membrane, adhésion, Candida albicans, lcsh:Science, Recombination, Genetic, 0303 health sciences, Fungal protein, Multidisciplinary, cell wall, protein, Rbt1, adhesion, biology, Flow Cytometry, 3. Good health, Cell biology, Transport protein, Protein Transport, medicine.anatomical_structure, protéine, paroi cellulaire, Hydrophobic and Hydrophilic Interactions, Research Article, Protein domain, Saccharomyces cerevisiae, Hyphae, Fungal Proteins, Structure-Activity Relationship, 03 medical and health sciences, Cell Adhesion, medicine, Humans, Amino Acid Sequence, Cell adhesion, 030304 developmental biology, Sequence Homology, Amino Acid, 030306 microbiology, Cell Membrane, lcsh:R, fungi, biology.organism_classification, Protein Structure, Tertiary, Membrane protein, Biofilms, Polystyrenes, lcsh:Q
Abstract

Cell wall proteins are central to the virulence of Candida albicans. Hwp1, Hwp2 and Rbt1 form a family of hypha-associated cell surface proteins. Hwp1 and Hwp2 have been involved in adhesion and other virulence traits but Rbt1 is still poorly characterized. To assess the role of Rbt1 in the interaction of C. albicans with biotic and abiotic surfaces independently of its morphological state, heterologous expression and promoter swap strategies were applied. The N-terminal domain with features typical of the Flo11 superfamily was found to be essential for adhesiveness to polystyrene through an increase in cell surface hydrophobicity. A 42 amino acid-long domain localized in the central part of the protein was shown to enhance the aggregation function. We demonstrated that a VTTGVVVVT motif within the 42 amino acid domain displayed a high beta-aggregation potential and was responsible for cell-to-cell interactions by promoting the aggregation of hyphae. Finally, we showed through constitutive expression that while Rbt1 was directly accessible to antibodies in hyphae, it was not so in yeast. Similar results were obtained for another cell wall protein, namely Iff8, and suggested that modification of the cell wall structure between yeast and hyphae can regulate the extracellular accessibility of cell wall proteins independently of gene regulation.

Published
2013

33. 2-Arylbenzofuran-based molecules as multipotent Alzheimer's disease modifying agents

Author

Vincenzo Di Marzo, Silvia Gobbi, Federica Belluti, Andrea Tarozzi, Angela Rampa, Stefano Rizzo, Marco Allarà, Alessandra Bisi, Manuela Bartolini, Grégory Da Costa, Patrizia Hrelia, Alessia Ligresti, Jean-Pierre Monti, Vincenza Andrisano, S. Rizzo, A. Tarozzi, M. Bartolini, G. Da Costa, A. Bisi, S. Gobbi, F. Belluti, A. Ligresti, M. Allarà, J-P. Monti, V. Andrisano, V. Di Marzo, P. Hrelia, and A. Rampa

Subjects
Cannabinoid receptor, Cell Survival, Aché, drug design, medicine.medical_treatment, Disease, Pharmacology, Neuroprotection, Cell membrane, Structure-Activity Relationship, chemistry.chemical_compound, Alzheimer Disease, Cell Line, Tumor, Drug Discovery, medicine, Humans, Benzofurans, Amyloid beta-Peptides, Dose-Response Relationship, Drug, Molecular Structure, Organic Chemistry, Neurotoxicity, General Medicine, medicine.disease, language.human_language, medicine.anatomical_structure, chemistry, Abeta peptide, Butyrylcholinesterase, 2-arylbenzofuran, Acetylcholinesterase, language, CB receptors, neuroprotection, Cholinesterase Inhibitors, Cannabinoid, Lead compound, Alzheimer’s disease
Abstract

The complex etiology of Alzheimer's disease prompts scientists to develop multi-target strategies to combat causes and symptoms. In line with this modern paradigm and as a follow-up to our previous studies, we designed and synthesized a focused collection of new 2-arylbenzofurans and evaluated their biological properties towards specific targets involved in AD, namely human AChE and human BuChE, and Aβ fibril formation. Selected compounds were also tested for their ability to inhibit Aβ neurotoxicity in terms of neuronal viability loss, and to prevent Aβ peptide-binding to cell membrane and intracellular reactive oxygen species (ROS) formation. The different modifications introduced in the structure of our lead compound led to an increase in activity towards one or more of the selected targets: the anticholinesterase activity of some compounds was found to be significantly higher than previously obtained related molecules, and the compounds also proved to possess Aβ anti-aggregating properties and neuroprotective effects. The most interesting multi-target compounds were 18, and 1. Interestingly, 1 also showed good selectivity and moderate affinity for CB1 receptor, opening new perspectives in the field of research on AD, since cannabinoid ligands have been widely reported to have neuroprotective properties.

Published
2012

34. Spin Distribution in Electron-Rich Piano-Stool Iron(III) Pyridylalkynyl Radical Cations Containing [(eta(2)-dppe)(eta(5)-C5Me5)FeC C](+) End Groups

Author

Gilles Argouarch, Arnaud Bondon, Loïc Toupet, Floriane Malvolti, Sourisak Sinbandhit, Frédéric Paul, Sylvie Le Stang, Grégory Da Costa, Claude Lapinte, Frédéric Justaud, Karine Costuas, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Plate-forme Rennaise d'Imagerie et Spectroscopie Structurale et Métabolique (PRISM), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Physique de Rennes (IPR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)

Subjects
010405 organic chemistry, Organic Chemistry, Substituent, Electronic structure, 010402 general chemistry, Ring (chemistry), 01 natural sciences, 0104 chemical sciences, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Inorganic Chemistry, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, chemistry.chemical_compound, Crystallography, Paramagnetism, chemistry, Mössbauer spectroscopy, Halogen, Proton NMR, Electronic effect, Organic chemistry, Physical and Theoretical Chemistry, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract

International audience; This experimental and theoretical contribution is aimed at investigating the electronic structure of cationic electron-rich ethynylpyridyl Fe(III) derivatives of the formula [(η2-dppe)(η5-C5Me5)FeC≡C(x-C5H4N)][PF6] (x = 4, 3, 2; 1a−c[PF6]) and [(η2-dppe)(η5-C5Me5)FeC≡C(2,5-C5H3NX)][PF6] (X = Cl, Br; 2a,b[PF6]). The Mössbauer, NMR, and ESR characterization of these paramagnetic species are reported and discussed in connection with DFT results. Special emphasis is put on the electronic effect of the nitrogen atom and of the halogen substituent on the spin distribution within the pyridyl unit. It is shown that 1H NMR constitutes a straightforward empirical way to investigate the slight changes in spin distribution taking place on the heteroaryl ring.

Published
2010

35. Topological dependence of the magnetic exchange coupling in arylethynyl-bridged organometallic diradicals containing [(eta(2)-dppe)(eta(5)-C(5)Me(5))Fe(III)](+) fragments

Author

Floriane Malvolti, Grégory Da Costa, Sourisak Sinbandhit, Loïc Toupet, Karine Costuas, Marie-Laure Boillot, Olivier Cador, Arnaud Bondon, Frédéric Paul, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Plate-forme Rennaise d'Imagerie et Spectroscopie Structurale et Métabolique (PRISM), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Interactions cellulaires et moléculaires (ICM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique de Rennes (IPR), Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), CNRS, De Villemeur, Hervé, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Biphenyl, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [CHIM.INOR] Chemical Sciences/Inorganic chemistry, Spins, 010405 organic chemistry, Diradical, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Inorganic Chemistry, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, chemistry.chemical_compound, Crystallography, chemistry, Unpaired electron, Ferromagnetism, Computational chemistry, Intramolecular force, Density functional theory, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Singlet state, Physical and Theoretical Chemistry
Abstract

International audience; We have investigated the spin distribution and determined the magnetic exchange coupling J(ab) (defined according to the following Hamiltonian: H(spin) = -2J(ab)S(a).S(b)) for three arylethynyl-bridged organoiron(III) diradicals containing [(eta(2)-dppe)(eta(5)-C(5)Me(5))Fe(III)](+) fragments. Considering the distance separating the Fe(III) centers (>or=11 A), remarkably large intramolecular magnetic interactions between unpaired spins were found for two of them. Thus, an antiferromagnetic coupling (J(ab)) of ca. -190 cm(-1) was experimentally determined for the binuclear Fe(III) species featuring a 1,4-diethynylbenzene bridge 1[PF(6)](2), while a ferromagnetic interaction of over +150 cm(-1) was evidenced for its 1,3-substitued analogue 2[PF(6)](2). We also show that a much weaker interaction (0 > J(ab) >or= -1 cm(-1)) takes place in the 4,4'-biphenyl analogue of 1[PF(6)](2) (3[PF(6)](2)), evidencing that insertion of an additional 1,4-phenylene unit in the bridge severely disrupts the magnetic communication in these diradicals. With the help of NMR and density functional theory, the magnetic properties of these compounds were rationalized and compared to those of the corresponding mononuclear Fe(III) relatives 4[PF(6)] and 5[PF(6)]. Finally, it is shown that, for all of these dinuclear Fe(III) complexes, the structural changes between singlet and triplet spin isomers remain very small regarding the carbon-rich bridge. Thus, even for a strongly coupled diradical such as 1[PF(6)](2), a dominant diradicaloid character dominates the valence-bond description of the singlet state unpaired electrons.

Published
2009

36. Ambient pH signalling in the yeast Yarrowia lipolytica involves YlRim23p/PalC, which interacts with Snf7p/Vps32p, but does not require the long C terminus of YlRim9p/PalI

Author

Claude Gaillardin, Grégory Da Costa, Sylvie Blanchin-Roland, Microbiologie et Génétique Moléculaire (MGM), and Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Signal Transduction, MESH: Hydrogen-Ion Concentration, MESH: Mutation, Saccharomyces cerevisiae, Mutant, Yarrowia, transduction du signal, signal pH, MESH: Reproduction, MESH: Two-Hybrid System Techniques, Microbiology, ESCRT, Fungal Proteins, 03 medical and health sciences, Aspergillus nidulans, Gene Expression Regulation, Fungal, Two-Hybrid System Techniques, MESH: Protein Binding, Candida albicans, levure, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Reproduction, C-terminus, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hydrogen-Ion Concentration, biology.organism_classification, Yeast, Biochemistry, Mutation, MESH: Fungal Proteins, MESH: Yarrowia, yarrowia lipolytica, MESH: Gene Expression Regulation, Fungal, Protein Binding, Signal Transduction
Abstract

International audience; A conserved ambient pH signal transduction pathway has been evidenced in both ascomycetous yeasts and filamentous fungi, called the Rim or Pal pathway, respectively. However, closely related PalC orthologues are found only in Yarrowia lipolytica and in filamentous fungi, where the Rim9p/PalI factor has a much longer C-terminal tail than in other yeasts. We show here that, like Aspergillus nidulans palI mutants, a Ylrim9Delta mutant has a less extreme phenotype than other mutants of the pathway, whereas rim9 mutants in Saccharomyces cerevisiae and Candida albicans reportedly exhibit a tight Rim phenotype. Deletion of the long C-terminal tail of YlRim9p/PalI had no phenotypic effect on ambient pH signalling. We also show that the Y. lipolytica PalC orthologue, named YlRim23p, is absolutely required for the alkaline pH response. Its only interactant identified in a genome-wide two-hybrid screen is YlSnf7/Vps32p, confirming the link between the Rim and the Vps pathways. YlRim13p and YlRim20p both interact with YlSnf7/Vps32p but not with YlRim23p. The long C-terminal tail of YlRim9p/PalI interacts neither with YlRim23p nor with YlSnf7/Vps32p. These results show that YlRim23p is a bona fide component of the Rim pathway in Y. lipolytica and that it participates in the complexes linking pH signalling and endocytosis.

Published
2008

37. Spin Distribution in Electron-rich Iron (III) Acetylides: ESR, NMR and DFT Study of Mononuclear Model Complexes

Author

Frédéric Paul, Gauthier, N., Grégory da Costa, Arnaud Bondon, Jy Thepot, Karine Costuas, Loic Toupet, Jean-François Halet, Lapinte, C., Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique de Rennes (IPR), De Villemeur, Hervé, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, stomatognathic diseases, InformationSystems_MODELSANDPRINCIPLES, ComputingMilieux_THECOMPUTINGPROFESSION, GeneralLiterature_INTRODUCTORYANDSURVEY, ComputingMilieux_COMPUTERSANDEDUCATION, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract

Communication orale

Published
2007

38. Binding of the dystrophin second repeat to membrane di-oleyl phospholipids is dependent upon lipid packing

Author

Corinne Rondeau-Mouro, Liza Mouret, Sandrine Pottier, Marie Fourage, Chantal Rocher, Grégory Da Costa, Elisabeth Le Rumeur, Arnaud Bondon, Laurent Metzinger, Interactions cellulaires et moléculaires (ICM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Repetitive Sequences, Amino Acid, Vesicle-associated membrane protein 8, Light, Static Electricity, Biophysics, Protein–lipid interaction, Biochemistry, Dystrophin, Membrane Lipids, 03 medical and health sciences, chemistry.chemical_compound, Escherichia coli, Humans, Scattering, Radiation, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cytoskeleton, Phospholipids, Unilamellar Liposomes, 030304 developmental biology, Phosphatidylethanolamine, 0303 health sciences, biology, Chemistry, Vesicle, 030302 biochemistry & molecular biology, Spectrin repeat, Cell Biology, Hydrogen-Ion Concentration, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Membrane protein, biology.protein, Membrane packing
Abstract

International audience; Dystrophin is the genetically deficient protein in Duchenne Muscular Dystrophy. Its C- and N-terminal ends interact with cytoskeletal and membrane proteins, establishing a link between the cytoskeleton and the extracellular matrix. In a previous study, we showed that there is an interaction between the second repeat of the rod domain and membrane phospholipids, which places tryptophan residues in close contact with the membrane. Here, we examine the binding of the dystrophin repeat-2 to small unilamellar vesicles with varying composition. We find that the protein binds predominantly to di-oleyl-phosphatidylserine. The binding as a function of increasing mol% of DOPS appears to be cooperative due to reduction of dimensionality, greatly enhanced in the absence of salts, and partly modulated by pH. Substituting small by large unilamellar vesicles induces a 30-fold lower affinity of the protein for the membrane phospholipids. However, modifying the packing of the acyl chains by introducing lipids such as phosphatidylethanolamine and cholesterol to the vesicle leads to an approximately 7-fold increase in affinity. Taken together, these results show that the binding involves electrostatic forces in addition to hydrophobic ones.

Published
2007

39. ESCRT-I components of the endocytic machinery are required for Rim101-dependent ambient pH regulation in the yeast Yarrowia lipolytica

Author

Grégory Da Costa, Claude Gaillardin, Sylvie Blanchin-Roland, Microbiologie et Génétique Moléculaire (MGM), Institut National de la Recherche Agronomique (INRA)-Institut National Agronomique Paris-Grignon (INA P-G)-Centre National de la Recherche Scientifique (CNRS), and Institut National Agronomique Paris Grignon (INAPG)

Subjects
Saccharomyces cerevisiae Proteins, Endocytic cycle, Molecular Sequence Data, Vesicular Transport Proteins, Yarrowia, Endosomes, macromolecular substances, Endocytosis, Microbiology, ESCRT, Insertional mutagenesis, Fungal Proteins, MULTIVESICULAR BODY, 03 medical and health sciences, Gene Expression Regulation, Fungal, Transport Vesicles, Gene, 030304 developmental biology, 0303 health sciences, biology, Endosomal Sorting Complexes Required for Transport, ENDOSOME, 030306 microbiology, Nuclear Proteins, Sequence Analysis, DNA, Hydrogen-Ion Concentration, biology.organism_classification, Yeast, YARROWIA LIPOLYTICA, PH REGULATION, ESCRT complex, DNA-Binding Proteins, ESCRT-I, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, MVB, Mutation, ALKALINE REPONSE
Abstract

Ambient pH signalling involves a cascade of conserved Rim or Pal products in ascomycetous yeasts or filamentous fungi, respectively. Insertional mutagenesis in the yeastYarrowia lipolyticaidentified two components of the endosome-associated ESCRT-I complex involved in multivesicular body (MVB) vesicle formation, YlVps28p and YlVps23p. They were shown to be required at alkaline pH, like Rim factors, for transcriptional activation of alkaline-induced genes and repression of acid-induced genes. The constitutively activeYlRIM101-1119allele, which suppresses the pH-signalling defects ofYlrimmutations, also suppressesYlvpsdefects in pH response, but not in endocytosis. The contribution of the ESCRT-III component Snf7p could not be assessed due to the essential nature of this component inY. lipolytica. Unlike Rim factors, YlVps4p, a component of the MVB pathway acting downstream from ESCRT complexes, seems not to be required for the alkaline response. InY. lipolytica, allvpsmutations including those affectingYlVPS4, affected growth at acidic pH, a feature not exhibited byYlrimmutations. These results suggest that Rim and Vps pathways cooperate in ambient pH signalling and that this relation is conserved across the full range of hemiascomycetous yeasts.

Published
2005

40. Effects of Five Filamentous Fungi Used in Food Processes on In Vitro and In Vivo Gut Inflammation

Author

Maxime Poirier, Cindy Hugot, Madeleine Spatz, Gregory Da Costa, Alexia Lapiere, Chloé Michaudel, Camille Danne, Valérie Martin, Philippe Langella, Marie-Laure Michel, Harry Sokol, Patrick Boyaval, and Mathias L. Richard

Subjects
gut microbiota, inflammatory bowel disease, molds, Biology (General), QH301-705.5
Abstract

Food processes use different microorganisms, from bacteria to fungi. Yeast strains have been extensively studied, especially Saccharomyces cerevisiae. However, to date, very little is known about the potential beneficial effects of molds on gut health as part of gut microbiota. We undertook a comprehensive characterization of five mold strains, Penicillium camemberti, P. nalgiovense, P. roqueforti, Fusarium domesticum, and Geotrichum candidum used in food processes, on their ability to trigger or protect intestinal inflammation using in vitro human cell models and in vivo susceptibility to sodium dextran sulfate-induced colitis. Comparison of spore adhesion to epithelial cells showed a very wide disparity in results, with F. domesticum and P. roqueforti being the two extremes, with almost no adhesion and 20% adhesion, respectively. Interaction with human immune cells showed mild pro-inflammatory properties of all Penicillium strains and no effect of the others. However, the potential anti-inflammatory abilities detected for G. candidum in vitro were not confirmed in vivo after oral gavage to mice before and during induced colitis. According to the different series of experiments carried out in this study, the impact of the spores of these molds used in food production is limited, with no specific beneficial or harmful effect on the gut.

Published
2022
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41. Gallotannins and Tannic Acid: First Chemical Syntheses and In Vitro Inhibitory Activity on Alzheimer's Amyloid b-Peptide Aggregation.

Author

Sylla, Tahiri, Pouységu, Laurent, Grégory Da Costa, Deffieux, Denis, Monti, Jean-Pierre, and Quideau, Stéphane

Subjects
GALLOTANNIN, TANNINS, CHEMICAL synthesis, AMYLOID beta-protein, POLYPHENOLS, ALZHEIMER'S disease
Abstract

The screening of natural products in the search for new lead compounds against Alzheimer's disease has unveiled several plant polyphenols that are capable of inhibiting the formation of toxic β-amyloid fibrils. Gallic acid based gallotannins are among these polyphenols, but their antifibrillogenic activity has thus far been examined using "tannic acid", a commercial mixture of gallotannins and other galloylated glucopyranoses. The first total syntheses of two true gallotannins, a hexagalloylglucopyranose and a decagalloylated compound whose structure is commonly used to depict "tannic acid", are now described. These depsidic gallotannins and simpler galloylated glucose derivatives all inhibit amyloid β-peptide (Aβ) aggregation in vitro, and monogalloylated αa-glucogallin and a natural β-hexagalloylglucose are shown to be the strongest inhibitors. [ABSTRACT FROM AUTHOR]

Published
2015
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42. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice

Author

Jane M. Natividad, Bruno Lamas, Hang Phuong Pham, Marie-Laure Michel, Dominique Rainteau, Chantal Bridonneau, Gregory da Costa, Johan van Hylckama Vlieg, Bruno Sovran, Celia Chamignon, Julien Planchais, Mathias L. Richard, Philippe Langella, Patrick Veiga, and Harry Sokol

Subjects
Science
Abstract

Lipid intake is known to promote Bilophila wadsworthia growth. Here the authors show that B. wadsworthia aggravates high fat diet induced metabolic dysfunctions and its suppression, both pharmacologically or mediated by Lactobacillus rhamnosus, limits the severity of metabolic impairment.

Published
2018
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43. 1H-NMR Metabolomics as a Tool for Winemaking Monitoring

Author

Inès Le Mao, Jean Martin-Pernier, Charlyne Bautista, Soizic Lacampagne, Tristan Richard, and Gregory Da Costa

Subjects
1H-NMR, metabolomics, wine, winemaking, Organic chemistry, QD241-441
Abstract

The chemical composition of wine is known to be influenced by multiple factors including some viticulture practices and winemaking processes. 1H-NMR metabolomics has been successfully applied to the study of wine authenticity. In the present study, 1H-NMR metabolomics in combination with multivariate analysis was applied to investigate the effects of grape maturity and enzyme and fining treatments on Cabernet Sauvignon wines. A total of forty wine metabolites were quantified. Three different stages of maturity were studied (under-maturity, maturity and over-maturity). Enzyme treatments were carried out using two pectolytic enzymes (E1 and E2). Finally, two proteinaceous fining treatments were compared (vegetable protein, fining F1; pea protein and PVPP, fining F2). The results show a clear difference between the three stages of maturity, with an impact on different classes of metabolites including amino acids, organic acids, sugars, phenolic compounds, alcohols and esters. A clear separation between enzymes E1 and E2 was observed. Both fining agents had a significant effect on metabolite concentrations. The results demonstrate that 1H-NMR metabolomics provides a fast and robust approach to study the effect of winemaking processes on wine metabolites. These results support the interest to pursue the development of 1H-NMR metabolomics to investigate the effects of winemaking on wine quality.

Published
2021
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44. Spin Delocalization in Electron-Rich Iron(III) Piano-Stool -Acetylides. An Experimental (NMR) and Theoretical (DFT) Investigation.

Author

Frédéric Paul, Grégory da Costa, Arnaud Bondon, Nicolas Gauthier, Sourisak Sinbandhit, Loic Toupet, Karine Costuas, Jean-François Halet, and Claude Lapinte

Subjects
*PROTONS, *RELAXATION phenomena, *NUCLEAR magnetic resonance, *BARYONS, *PHYSICAL & theoretical chemistry
Abstract

Several paramagnetic electron-rich Fe(III) mononuclear arylacetylide complexes of formula (2-dppe)(5-C5Me5)Fe(CC−Ar)in which Ar represents a functional aryl group were studied by means of multinuclear NMR. All signals detected for the various nuclei were assigned. Hyperfine coupling constants for selected nuclei of the arylacetylide ligand were derived from 1H or 19F NMR contact shifts. These NMR data are diagnostic of a metal-centered unpaired electron partly residing in a molecular orbital on the arylacetylide ligand, in line with DFT computations. We show here that the 1H NMR paramagnetic shifts of the ortho (H1) and meta (H2) arylacetylide protons convey decisive information on the charge distribution in the aryl ring. Estimates of the relaxation rates of the unpaired electron were also derived from half-widths of the 1H NMR signals. Finally, line-broadening studies of Fe(II)/Fe(III) mixtures allowed extracting the self-exchange rates for several redox couples among these complexes. The self-exchange rates appear slightly substituent dependent and are apparently larger for compounds with electron-withdrawing substituents on the aryl ring. Reorganization energies of ca. 4000 cm-1could be derived for these outer-sphere electron-transfer processes. [ABSTRACT FROM AUTHOR]

Published
2007
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45. New C-Glycosidic Ellagitannins Formed upon Oak Wood Toasting, Identification and Sensory Evaluation

Author

Kleopatra Chira, Laura Anguellu, Gregory Da Costa, Tristan Richard, Eric Pedrot, Michael Jourdes, and Pierre-Louis Teissedre

Subjects
ellagitannins, toasting, oak wood, astringency, bitterness, Chemical technology, TP1-1185
Abstract

In the courses of studies on ellagitannin changes during oak wood toasting, two C-glycosidic ellagitannins were isolated from the french oak wood for the first time. These two compounds exhibited [M−H]− ion peak at m/z 1055.0631 (compound A) and at m/z 1011.0756 (compound B). A compound is named Castacrenin E and is produced by Castacrenin D oxidation. Castacrenin D is a vescalagin with an additional aromating ring to the C-1 through a C-C bond. These compounds are not only found under laboratory conditions but also in commercial oak wood representing different toasting methods and sizes. Their levels are conditioned by oak wood dimensions and toasting degree. The wood pieces with the smallest size present almost two times more compounds A and B. Moreover, the compound B is the only compound to be present in medium toasting temperatures of the smallest wood pieces. Both of them can influence either astringency sensation or bitterness taste.

Published
2020
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46. Functional analysis of Candida albicans GPI-anchored proteins: Roles in cell wall integrity and caspofungin sensitivity

Author

Louise E. Walker, Neil A. R. Gow, Grégory Da Costa, Héctor M. Mora-Montes, Armêl Plaine, Mathias L. Richard, Claude Gaillardin, Carol A. Munro, and Alastair D. McKinnon

Subjects
Antifungal Agents, Glycosylphosphatidylinositols, Saccharomyces cerevisiae, Chitin, Calcofluor-white, Microbiology, Article, Fungal Proteins, Cell wall, Echinocandins, Lipopeptides, 03 medical and health sciences, chemistry.chemical_compound, Caspofungin, Glycosyltransferase, Candida albicans, Genetics, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Calcofluor, Chlamydospore formation, biology.organism_classification, Corpus albicans, Surface, chemistry, Biochemistry, GPI, biology.protein
Abstract

The outer layer of the Candida albicans cell wall is enriched in highly glycosylated proteins. The major class, the GlycosylPhosphatidylInositol (GPI)-anchored proteins are tethered to the wall by GPI-anchor remnants and include adhesins, glycosyltransferases, yapsins and superoxide dismutases. In silico analysis suggested that C. albicans possesses 115 putative GPI anchored proteins (GpiPs), almost twice the number reported for Saccharomyces cerevisiae. A global approach to characterise in silico predicted GpiPs has been initiated by generating a library of 45 mutants. This library was subjected to a screen for cell wall modifications by testing the cell wall integrity (SDS and Calcofluor White sensitivity) and response to caspofungin. We showed that, when caspofungin sensitivity was modified, in more than half of the cases the susceptibility can be correlated to the level of chitin and cell wall thickness: sensitive strains have low level of chitin and a thin cell wall. We also identified, for the first time, genes that when deleted lead to decreased caspofungin sensitivity: DFG5, PHR1, PGA4 and PGA62. The role of two unknown GpiPs, Pga31 and Pga62 in the cell wall structure and composition was clearly demonstrated during this study.

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