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7 results on '"Inserm (UMR 1071)"'

1. Genes mcr improve the intestinal fitness of pathogenic E. coli and balance their lifestyle to commensalism

Author

Guillaume Dalmasso, Racha Beyrouthy, Sandrine Brugiroux, Etienne Ruppé, Laurent Guillouard, Virginie Bonnin, Pierre Saint-Sardos, Amine Ghozlane, Vincent Gaumet, Nicolas Barnich, Julien Delmas, Richard Bonnet, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), This study was supported by the Ministère de la Recherche et de la Technologie, the Inserm (UMR 1071), the INRAe (USC-2018), the French government’s IDEX-ISITE initiative 16-IDEX-0001 (CAP 20-25), the National Program ‘Microbiote’ Inserm, the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) programme TransComp-ESC-R of the European Commission, and a grant (‘DYASPEO’) from the national priority research program for antimicrobial resistance (PPR-AMR)., ANR-20-PAMR-0003,DYASPEO,Dynamics, AMR, spread, persistence, evolution, colonization, human, animal, environment(2020), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), and European Project: 323209,EC:FP7:HEALTH,FP7-JPROG-2012-RTD,JPIAMR(2012)

Subjects
Microbiology (medical), Inflammation, Virulence, Colistin, Antibiotic resistance, Microbiota, [SDV]Life Sciences [q-bio], Escherichia coli, Antimicrobial peptides, mcr-1, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Microbiology, Commensalism
Abstract

Background The plasmid-mediated resistance gene mcr-1 confers colistin resistance in Escherichia coli and paves the way for the evolution to pan-drug resistance. We investigated the impact of mcr-1 in gut colonization in the absence of antibiotics using isogenic E. coli strains transformed with a plasmid encoding or devoid of mcr-1. Results In gnotobiotic and conventional mice, mcr-1 significantly enhanced intestinal anchoring of E. coli but impaired their lethal effect. This improvement of intestinal fitness was associated with a downregulation of intestinal inflammatory markers and the preservation of intestinal microbiota composition. The mcr-1 gene mediated a cross-resistance to antimicrobial peptides secreted by the microbiota and intestinal epithelial cells (IECs), enhanced E. coli adhesion to IECs, and decreased the proinflammatory activity of both E. coli and its lipopolysaccharides. Conclusion Overall, mcr-1 changed multiple facets of bacterial behaviour and appeared as a factor enhancing commensal lifestyle and persistence in the gut even in the absence of antibiotics.

Published
2023

2. Successful dissemination of plasmid-mediated extended-Spectrum β-lactamases in enterobacterales over humans to wild fauna

Author

Richard Bonnet, Frédéric Robin, Patrícia Poeta, Racha Beyrouthy, Giberto Igrejas, Carolina Sabença, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Universidade de Trás-os-Montes e Alto Douro (UTAD), Universidade do Trás-os-Montes e Alto Douro, Laboratorio Associado para a Quimica Verde (LAQV), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto, Ministere de la Recherche et de la Technologie, Inserm (UMR 1071), INRAe (USC-2018), Programa de Accoes Universitarias Integradas Luso-Francesas [TC-14/2017], Portuguese Foundation for Science and Technology [[UID/QUI/50006/2019], ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), European Project: 323209,EC:FP7:HEALTH,FP7-JPROG-2012-RTD,JPIAMR(2012), Molé, Christine, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Coordination Action for the early implementation of the Joint Programming Initiative on Antimicrobial Resistance - JPIAMR - - EC:FP7:HEALTH2012-09-01 - 2016-02-29 - 323209 - VALID, Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)

Subjects
Microbiology (medical), QH301-705.5, medicine.disease_cause, Microbiology, Genome, Article, 03 medical and health sciences, Plasmid, Polymorphism (computer science), Virology, plasmid, medicine, Escherichia coli, IncI1-ST3, CTX-M-1, Biology (General), Gene, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Synteny, 2. Zero hunger, Genetics, 0303 health sciences, biology, 030306 microbiology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, β-lactamase, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Multilocus sequence typing, beta-lactamase, Bacteria
Abstract

Background: The emergence of multidrug-resistant bacteria remains poorly understood in the wild ecosystem and at the interface of habitats. Here, we explored the spread of Escherichia coli containing IncI1-ST3 plasmid encoding resistance gene cefotaximase-Munich-1 (blaCTX-M-1) in human-influenced habitats and wild fauna using a genomic approach. Methods. Multilocus sequence typing (MLST), single-nucleotide polymorphism comparison, synteny-based analysis and data mining approaches were used to analyse a dataset of genomes and circularised plasmids. Results. CTX-M-1 E. coli sequence types (STs) were preferentially associated with ecosystems. Few STs were shared by distinct habitats. IncI1-ST3-blaCTX-M-1 plasmids are disseminated among all E. coli phylogroups. The main divergences in plasmids were located in a shuffling zone including blaCTX-M-1 inserted in a conserved site. This insertion hot spot exhibited diverse positions and orientations in a zone-modulating conjugation, and the resulting synteny was associated with geographic and biological sources. Conclusions. The ecological success of IncI1-ST3-blaCTX-M-1 appears less linked to the spread of their bacterial recipients than to their ability to transfer in a broad spectrum of bacterial lineages. This feature is associated with the diversity of their shuffling conjugation region that contain blaCTX-M-1. These might be involved in the resistance to antimicrobials, but also in their spread.

Published
2021

3. Beneficial Effects of Natural Mineral Waters on Intestinal Inflammation and the Mucosa-Associated Microbiota

Author

Michael Rodrigues, Sylvain Denis, Nicolas Barnich, Monique Alric, Danielle Faure-Imbert, C. Roques, Benoit Chassaing, Thierry Hanh, Caroline Chevarin, Olivier Le Goff, Pierre Sauvanet, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre Suisse d'Electronique et de Microtechnique SA [Neuchatel] (CSEM), Centre Suisse d'Electronique et Microtechnique SA (CSEM), AllNext Consultants, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 'AFRETH' (Association francaise pour la recherche thermale) 2013-042021-02Ministere de la Recherche et de la Technologie INRAE (USC-2018) French government IDEX-ISITE initiative 16-IDEX-0001 (CAP 20-25)I-SITE project (CAP 2025) of the University of Clermont Auvergne European Research Council (ERC)ERC-2018-StG-804135Kenneth Rainin Foundation Inserm (UMR 1071), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Université de Toulouse (UT), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, Mice, chemistry.chemical_compound, 0302 clinical medicine, intestinal inflammation, mucosa-associated microbiota, Intestinal Mucosa, Biology (General), Spectroscopy, Mice, Inbred BALB C, Dextran Sulfate, General Medicine, Colitis, natural mineral water, 3. Good health, Computer Science Applications, Chemistry, Cytokine, Cytokines, 030211 gastroenterology & hepatology, medicine.symptom, QH301-705.5, Bicarbonate, Sodium, chemistry.chemical_element, Inflammation, Calcium, Article, Catalysis, Microbiology, Inorganic Chemistry, Lesion, 03 medical and health sciences, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Organic Chemistry, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, chemistry, Mineral Waters
Abstract

Natural mineral water (NMWs) intake has been traditionally used in the treatment of various gastrointestinal diseases. We investigated the effect of two French NMWs, one a calcium and magnesium sulphate, sodium chloride, carbonic, and ferruginous water (NMW1), the other a mainly bicarbonate water (NMW2) on the prevention of intestinal inflammation. Intestinal epithelial cells stimulated with heat inactivated Escherichia coli or H2O2 were treated with NMWs to evaluate the anti-inflammatory effects. Moderate colitis was induced by 1% dextran sulfate sodium (DSS) in Balbc/J mice drinking NMW1, NWW2, or control water. General signs and histological features of colitis, fecal lipocalin-2 and pro-inflammatory KC cytokine levels, global mucosa-associated microbiota, were analyzed. We demonstrated that both NMW1 and NMW2 exhibited anti-inflammatory effects using intestinal cells. In induced-colitis mice, NMW1 was effective in dampening intestinal inflammation, with significant reductions in disease activity scores, fecal lipocalin-2 levels, pro-inflammatory KC cytokine release, and intestinal epithelial lesion sizes. Moreover, NMW1 was sufficient to prevent alterations in the mucosa-associated microbiota. These observations, through mechanisms involving modulation of the mucosa-associated microbiota, emphasize the need of investigation of the potential clinical efficiency of such NMWs to contribute, in human beings, to a state of low inflammation in inflammatory bowel disease.

Published
2021

4. Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn’s disease

Author

Yann Guerardel, Pascal Vandekerckove, Shin-Yi Yu, Adeline Sivignon, Nathalie Ballet, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Lesaffre, Gifu University, Lesaffre international, Ministere de la Recherche et de la Technologie (Universite Clermont Auvergne), Inserm (UMR 1071), INRAE (USC-2018), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lille, CNRS, Lille Neurosciences & Cognition (LilNCog) - U 1172, and Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Subjects
Male, Phosphopeptides, Polymers and Plastics, Saccharomyces cerevisiae, Mannan-glucan heteropolysaccharides, Adherent-invasive Escherichia coli, Anti-adhesive strategy, NMR analysis, Mice, Transgenic, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Bacterial Adhesion, Microbiology, Cell wall, Mannans, 03 medical and health sciences, Feces, 0302 clinical medicine, Crohn Disease, In vivo, Cell Wall, Materials Chemistry, medicine, Escherichia coli, Animals, Glucans, 030304 developmental biology, Mannan, 0303 health sciences, biology, Chemistry, Organic Chemistry, Fungal Polysaccharides, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Yeast, In vitro, 3. Good health, Anti-Bacterial Agents, Gastrointestinal Microbiome, [CHIM.POLY]Chemical Sciences/Polymers, 030211 gastroenterology & hepatology, Female, Bacteria
Abstract

International audience; The Saccharomyces cerevisiae CNCM I-3856 was previously reported to strongly inhibit adherent-invasive Escherichia coli (AIEC) adhesion to intestinal epithelial cells in vitro and to favor AIEC elimination from the gut in a murine model of Crohn's disease in vivo. In order to identify which cell wall components of yeast are responsible for AIEC elimination, constituent polysaccharides of yeast were isolated and their anti-adhesive ability against AIEC adhesion in vitro was screened. A fraction containing mannan, β-glucan and α-glucan extracted from yeast cell-walls was shown to inhibit 95% of AIEC adhesion in vitro and was thus identified as the strongest anti-adhesive yeast cell wall component. Furthermore, this mannan-glucan-containing fraction was shown to accelerate AIEC decolonization from gut in vivo. This fraction could be proposed as a treatment to eliminate AIEC bacteria in patients with Crohn's disease, a microbial trigger of intestinal inflammation.

Published
2021

5. When adherent-invasive E. coli plays with host glycosylation: Does it open new perspectives for therapeutic strategies in Crohn's disease?

Author

Jérémy Denizot, Nicolas Barnich, Molé, Christine, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ministere de la Recherche et de la Technologie, Inserm (UMR 1071), INRAE (USC-2018), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)

Subjects
MESH: Glycomics, Glycosylation, Research paper, UDP-N-acetylglucosamine (UDP-GlcNAc), lcsh:Medicine, Biology, medicine.disease_cause, MESH: Protein Glycosylation, Bacterial Adhesion, NF-κB, General Biochemistry, Genetics and Molecular Biology, Crohn's disease (CD), Microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Crohn Disease, inflammatory bowel disease, MESH: Acute-Phase Reaction, Escherichia coli, medicine, Humans, MESH: Autophagy, Escherichia coli Infections, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Crohn's disease, lcsh:R5-920, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Crohn Disease, Crohn disease, Host (biology), MESH: Adherent Escherichia coli, lcsh:R, adherent-invasive Escherichia coli (AIEC) LF82, O-Linked β-N-acetylglucosamine (O-GlcNAc), General Medicine, medicine.disease, 3. Good health, carbohydrates (lipids), chemistry, 030220 oncology & carcinogenesis, Commentary, lcsh:Medicine (General), MESH: Celiac Disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Treatment of Crohn's disease (CD) remains to be a challenge due to limited insights for its pathogenesis. We aimed to determine the role of O-Linked β-N-acetylglucosamine (O-GlcNAc) in the development of CD and evaluate therapeutic effects of O-GlcNAc inhibitors on CD. Methods O-GlcNAc in intestinal epithelial tissues of CD, adherent-invasive Escherichia coli (AIEC) LF82-infected cells and mice was determined by immunoblot and immunohistochemistry. AIEC LF82 and dextran sulfate sodium were administrated into C57BL/6 mice for estabolishing inflammatory bowel disease model and for therapeutic study. Findings O-GlcNAc was increased in intestinal epithelial tissues of CD patients and AIEC LF82-infected mice. Infection of AIEC LF82 up-regulated the level of UDP-GlcNAc and increased O-GlcNAc in human colon epithelial HCT116 and HT-29 cells. We identified that IKKβ and NF-κB were O-Glycosylated in AIEC LF82-treated cells. Mutations of IKKβ (S733A) and p65 (T352A) abrogated the O-GlcNAc in IKKβ and NF-κB and inhibited AIEC LF82-induced activation of NF-κB. Application of 6-diazO-5-oxO-L-norleucine, an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAc, inactivated NF-κB in AIEC LF82-infected cells, enhanced the formation of autophagy, promoted the removal of cell-associated AIEC LF82, alleviated intestinal epithelial inflammation, and improved the survival of the colitis mice. Interpretation Intestinal inflammation in CD is associated with increased O-GlcNAc modification, which is required for NF-κB activation and suppression of autophagy. Targeting O-GlcNAc could be an effective therapy for inflammatory bowel disease. Funding National Natural Science Foundation of China (Nos. 81573087 and 81772924) and International Cooperation Foundation of Jilin Province (20190701006GH).

Published
2020

6. Impact of CDT Toxin on Human Diseases

Author

Tiphanie Faïs, Guillaume Dalmasso, Arnaud Serres, Julien Delmas, Richard Bonnet, ProdInra, Migration, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Hôpital Hôtel-Dieu de Clermont-Ferrand, CHU Clermont-Ferrand, and Ministere de la Recherche et de la Technologie, Institut national de la sante et de la recherche medicale (INSERM) UMR 1071, Institut national de la recherche agronomique (INRA) USC 2018

Subjects
0301 basic medicine, Campylobacterales, Gram-negative bacteria, Cytolethal distending toxin, Health, Toxicology and Mutagenesis, Aggregatibacter, Bacterial Toxins, lcsh:Medicine, composé organique, Review, Toxicology, CDT toxin, DNA damage, CDT-producing bacteria, Microbiology, 03 medical and health sciences, Bacterial Proteins, Risk Factors, Neoplasms, Gram-Negative Bacteria, Animals, Humans, Toxicologie, Inflammation, biology, Pasteurellaceae, lcsh:R, biology.organism_classification, Enterobacteriaceae, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, toxine, Cell Transformation, Neoplastic, 030104 developmental biology, bactérie gram négatif, physiologie cellulaire, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Host-Pathogen Interactions, Immunology, Actinobacillus, Inflammation Mediators, Gram-Negative Bacterial Infections, Haemophilus ducreyi
Abstract

International audience; Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects.

Published
2016

7. Glycopolymers as Antiadhesives of E. coli Strains Inducing Inflammatory Bowel Diseases

Author

Christophe Travelet, David Deniaud, Julien Bernard, Adeline Sivignon, Nicolas Barnich, Zhaoli Li, Etienne Fleury, Redouane Borsali, Nao Yamakawa, Arlette Darfeuille-Michaud, Agnes Crepet, Xibo Yan, Julie Bouckaert, Sébastien G. Gouin, Rostyslav Bilyy, Tetiana Dumych, Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE), Ministère de la Recherche et de la Technologie, Inserm (UMR 1071) and INRA (USC-2018), ANR-12-BSV5-0016,STARLET,Effets thérapeutiques de polymères mannosylés synthétiques capables de contrôler les infections chroniques ntestinales à Escherichia coli en interagissant avec la dynamique de glycosylation des cellules hôtes(2012), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de Chimie des polymères organiques (LCPO), Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Danylo Halytskiy Lviv National Medical University, Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Matériaux Polymères - Laboratoire des Matériaux Macromoléculaires (IMP-LMM), Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Synthèse Organique (Hétérochimie organique, organoéléments et matériaux) (LSOHOOM), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Recherche Agronomique (INRA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)

Subjects
Polymers and Plastics, Glycopolymer, Mannose, Bioengineering, Biology, medicine.disease_cause, Virulence factor, Microbiology, Biomaterials, chemistry.chemical_compound, Mice, Intestinal mucosa, Materials Chemistry, medicine, Cell Adhesion, Escherichia coli, [CHIM]Chemical Sciences, Animals, Humans, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, Adhesins, Escherichia coli, Polysaccharides, Bacterial, [CHIM.MATE]Chemical Sciences/Material chemistry, Inflammatory Bowel Diseases, In vitro, 3. Good health, Bacterial adhesin, [CHIM.POLY]Chemical Sciences/Polymers, Biochemistry, chemistry, Fimbriae Proteins, Ex vivo, Heptanol, HeLa Cells
Abstract

International audience; n-Heptyl alpha-D-mannose (HM) is a nanomolar antagonist of FimH, a virulence factor of E. coli. Herein we report on the construction of multivalent HM-based glycopolymers as potent antiadhesives of type 1 piliated E. coli. We investigate glycopolymer/FimH and glycopolymer/bacteria interactions and show that HM-based glycopolymers efficiently inhibit bacterial adhesion and disrupt established cell-bacteria interactions in vitro at very low concentration (0.1 mu M on a mannose unit basis). On a valency-corrected basis, HM-based glycopolymers are, respectively, 10(2) and 10(6) times more potent than HM and D-mannose for their capacity to disrupt the binding of adherent-invasive E. coli to T84 intestinal epithelial cells. Finally, we demonstrate that the antiadhesive capacities of HM-based glycopolymers are preserved ex vivo in the colonic loop of a transgenic mouse model of Crohns disease. All together, these results underline the promising scope of HM-based macromolecular ligands for the antiadhesive treatment of E. coli induced inflammatory bowel diseases.

Published
2015

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