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1. Characterization of a glycan-binding complex of minor pilins completes the analysis of Streptococcus sanguinis type 4 pili subunits

Author

Meriam Shahin, Devon Sheppard, Claire Raynaud, Jamie-Lee Berry, Ishwori Gurung, Lisete M. Silva, Ten Feizi, Yan Liu, Vladimir Pelicic, MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Microbiologie de la Méditerranée (IMM), Medical Research Council grant (MR/P022197/1), and Pelicic, Vladimir

Subjects
type 4 pili, [SDV] Life Sciences [q-bio], adhesion, Multidisciplinary, [SDV]Life Sciences [q-bio], pilin
Abstract

Type 4 filaments (T4F)—of which type 4 pili (T4P) are the archetype—are a superfamily of nanomachines nearly ubiquitous in prokaryotes. T4F are polymers of one major pilin, which also contain minor pilins whose roles are often poorly understood. Here, we complete the structure/function analysis of the full set of T4P pilins in the opportunistic bacterial pathogen Streptococcus sanguinis . We determined the structure of the minor pilin PilA, which is unexpectedly similar to one of the subunits of a tip-located complex of four minor pilins, widely conserved in T4F. We found that PilA interacts and dramatically stabilizes the minor pilin PilC. We determined the structure of PilC, showing that it is a modular pilin with a lectin module binding a subset of glycans prevalent in the human glycome, the host of S. sanguinis . Altogether, our findings support a model whereby the minor pilins in S. sanguinis T4P form a tip-located complex promoting adhesion to various host receptors. This has general implications for T4F.

Published
2022
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2. Time and age trends in smoking cessation in Europe

Author

Pesce, G, Marcon, A, Calciano, L, Perret, JL, Abramson, MJ, Bono, R, Bousquet, J, Fois, AG, Janson, C, Jarvis, D, Jogi, R, Leynaert, B, Nowak, D, Schlunssen, V, Urrutia-Landa, I, Verlato, G, Villani, S, Zuberbier, T, Minelli, C, Accordini, S, Boezen, M, Elger, B, Gleditsch, BA, Heijmans, B, Romieu, I, Thompson, J, Commission of the European Communities, Salvy-Córdoba, Nathalie, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University Hospital of Verona, Università degli studi di Verona = University of Verona (UNIVR), University of Melbourne, Monash University [Melbourne], Università degli studi di Torino = University of Turin (UNITO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università degli Studi di Sassari = University of Sassari [Sassari] (UNISS), Uppsala University Hospital, MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, University of Tartu, Ludwig Maximilian University [Munich] (LMU), Aarhus University Hospital, Galdakao Hospital, Università degli Studi di Pavia = University of Pavia (UNIPV), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Verona (UNIVR), University of Turin, University of Sassari, Università degli Studi di Pavia, Groningen Research Institute for Asthma and COPD (GRIAC), and Life Course Epidemiology (LCE)

Subjects
Male, Pulmonology, IMPACT, medicine.medical_treatment, Maternal Health, Tobacco Smoking / epidemiology, Social Sciences, RELAPSE, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Geographical Locations, Habits, INITIATION, 0302 clinical medicine, Elderly, Quality of life, Pregnancy, Smoking Habits, Medicine and Health Sciences, Medicine, Psychology, Public and Occupational Health, 030212 general & internal medicine, Young adult, PREDICTORS, 0303 health sciences, Multidisciplinary, Tobacco control, food and beverages, Obstetrics and Gynecology, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, 3. Good health, PREVALENCE, Europe, Multidisciplinary Sciences, ALLERGIC RHINITIS, Age trends, Ageing Lungs in European Cohorts (ALEC) study, Europe, smoking cessation, time trends, Science & Technology - Other Topics, Female, Public Health, Europe / epidemiology, Research Article, Adult, medicine.medical_specialty, Tobacco Control, Smoking Cessation / statistics & numerical data, Adolescent, Substance-Related Disorders, General Science & Technology, Science, Health Promotion, Age trends, 03 medical and health sciences, Young Adult, Age Distribution, Sex Factors, Public Health, Tobacco Control, Tobacco Smoking, Smoking Cessation, Time Trends, Pregnancy, Mental Health and Psychiatry, MD Multidisciplinary, Tobacco Smoking, Humans, Risk factor, 030304 developmental biology, time trends, Behavior, Science & Technology, business.industry, Public health, Biology and Life Sciences, Smoking Related Disorders, Retrospective cohort study, ADULTS, Ageing Lungs in European Cohorts (ALEC) study, smoking cessation, Young Adults, Health Care, Retrospective studies, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Health promotion, Age Groups, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, People and Places, Quality of Life, Smoking cessation, Women's Health, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, ASTHMA, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography
Abstract

BackgroundSmoking is the main risk factor for most of the leading causes of death. Cessation is the single most important step that smokers can take to improve their health. With the aim of informing policy makers about decisions on future tobacco control strategies, we estimated time and age trends in smoking cessation in Europe between 1980 and 2010.MethodsData on the smoking history of 50,228 lifetime smokers from 17 European countries were obtained from six large population-based studies included in the Ageing Lungs in European Cohorts (ALEC) consortium. Smoking cessation rates were assessed retrospectively, and age trends were estimated for three decades (1980-1989, 1990-1999, 2000-2010). The analyses were stratified by sex and region (North, East, South, West Europe).ResultsOverall, 21,735 subjects (43.3%) quit smoking over a total time-at-risk of 803,031 years. Cessation rates increased between 1980 and 2010 in young adults (16-40 years), especially females, from all the regions, and in older adults (41-60 years) from North Europe, while they were stable in older adults from East, South and West Europe. In the 2000s, the cessation rates for men and women combined were highest in North Europe (49.9 per 1,000/ year) compared to the other regions (range: 26.5-32.7 per 1,000/ year). A sharp peak in rates was observed for women around the age of 30, possibly as a consequence of pregnancy-related smoking cessation. In most regions, subjects who started smoking before the age of 16 were less likely to quit than those who started later.ConclusionsOur findings suggest an increasing awareness on the detrimental effects of smoking across Europe. However, East, South and West European countries are lagging behind North Europe, suggesting the need to intensify tobacco control strategies in these regions. Additional efforts should be made to keep young adolescents away from taking up smoking, as early initiation could make quitting more challenging during later life.

Published
2019
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3. Inhibition of the Staphylococcus aureus c-di-AMP cyclase DacA by direct interaction with the phosphoglucosamine mutase GlmM

Author

Rahul Kumar Singh, Delphine Patin, Dominique Mengin-Lecreulx, Charles Eldrid, Konstantinos Thalassinos, Tommaso Tosi, Charlotte Millership, Paul S. Freemont, Angelika Gründling, Fumiya Hoshiga, MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Institute of Structural and Molecular Biology (ISMB), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département Microbiologie (Dpt Microbio), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Enveloppes Bactériennes et Antibiotiques (ENVBAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Department of Medicine, Imperial College London, London, United Kingdom, Medical Research Council (MRC), and Wellcome Trust

Subjects
Operon, Staphylococcus, [SDV]Life Sciences [q-bio], domain, medicine.disease_cause, Pathology and Laboratory Medicine, Biochemistry, Second Messenger Systems, cyclic dinucleotide, X-Ray Diffraction, 1108 Medical Microbiology, Cell Wall, Medicine and Health Sciences, Macromolecular Structure Analysis, Transferase, Chemical Precipitation, Staphylococcus Aureus, Biology (General), Enzyme Chemistry, Materials, degradation, chemistry.chemical_classification, 0303 health sciences, Crystallography, Phosphoglucosamine mutase, Physics, 030302 biochemistry & molecular biology, Chemical Reactions, Pseudomonas Aeruginosa, Staphylococcal Infections, Condensed Matter Physics, 3. Good health, Bacterial Pathogens, Enzymes, mobility mass-spectrometry, Chemistry, 1107 Immunology, Medical Microbiology, Physical Sciences, Crystal Structure, integrity, Pathogens, Phosphorus-Oxygen Lyases, Crystallization, Life Sciences & Biomedicine, Dinucleoside Phosphates, 0605 Microbiology, Research Article, Adenylyl Cyclases, Methicillin-Resistant Staphylococcus aureus, Protein Structure, QH301-705.5, functional-analysis, growth, Immunology, Protein domain, Materials Science, bcs, Cyclase, Microbiology, Enzyme Regulation, resistance, 03 medical and health sciences, Bacterial Proteins, Protein Domains, Virology, Pseudomonas, Scattering, Small Angle, Genetics, medicine, Solid State Physics, Dimers, Escherichia coli, Microbial Pathogens, Molecular Biology, 030304 developmental biology, Science & Technology, Bacteria, Mutagenesis, Organisms, Biology and Life Sciences, Proteins, RC581-607, Polymer Chemistry, enzyme, Enzyme, chemistry, Phosphoglucomutase, Oligomers, Adenylyl Cyclase Inhibitors, Enzymology, Parasitology, Immunologic diseases. Allergy, scanning protein-a
Abstract

c-di-AMP is an important second messenger molecule that plays a pivotal role in regulating fundamental cellular processes, including osmotic and cell wall homeostasis in many Gram-positive organisms. In the opportunistic human pathogen Staphylococcus aureus, c-di-AMP is produced by the membrane-anchored DacA enzyme. Inactivation of this enzyme leads to a growth arrest under standard laboratory growth conditions and a re-sensitization of methicillin-resistant S. aureus (MRSA) strains to ß-lactam antibiotics. The gene coding for DacA is part of the conserved three-gene dacA/ybbR/glmM operon that also encodes the proposed DacA regulator YbbR and the essential phosphoglucosamine mutase GlmM, which is required for the production of glucosamine-1-phosphate, an early intermediate of peptidoglycan synthesis. These three proteins are thought to form a complex in vivo and, in this manner, help to fine-tune the cellular c-di-AMP levels. To further characterize this important regulatory complex, we conducted a comprehensive structural and functional analysis of the S. aureus DacA and GlmM enzymes by determining the structures of the S. aureus GlmM enzyme and the catalytic domain of DacA. Both proteins were found to be dimers in solution as well as in the crystal structures. Further site-directed mutagenesis, structural and enzymatic studies showed that multiple DacA dimers need to interact for enzymatic activity. We also show that DacA and GlmM form a stable complex in vitro and that S. aureus GlmM, but not Escherichia coli or Pseudomonas aeruginosa GlmM, acts as a strong inhibitor of DacA function without the requirement of any additional cellular factor. Based on Small Angle X-ray Scattering (SAXS) data, a model of the complex revealed that GlmM likely inhibits DacA by masking the active site of the cyclase and preventing higher oligomer formation. Together these results provide an important mechanistic insight into how c-di-AMP production can be regulated in the cell., Author summary c-di-AMP has recently emerged as an essential molecule in Gram-positive bacteria, controlling osmotic stress resistance and virulence. The molecule has also been linked to antibiotic resistance/sensitivity, as alterations in its levels have been shown to modulate the effect of cell wall-targeting antibiotics. c-di-AMP is produced and degraded by dedicated enzymes and the activities of these enzymes are tightly regulated in the cell for optimal bacterial growth. In the human pathogen Staphylococcus aureus, c-di-AMP is produced by the di-adenylate cyclase enzyme DacA, which is thought to form a complex and be regulated by YbbR and GlmM, two other conserved proteins. There are ongoing efforts to devise strategies to inhibit di-adenylate cyclase enzymes, as inhibition of c-di-AMP production will negatively impact bacterial growth and also re-sensitize methicillin-resistant S. aureus (MRSA) strains to ß-lactam antibiotics. Here, we investigated the activity and regulation of the S. aureus c-di-AMP cyclase DacA. We determined the atomic structures of the S. aureus DacA and GlmM enzymes and show that GlmM readily binds to DacA in vitro and blocks its activity by masking its active site. With this, our work provides important insight into possible ways to ablate c-di-AMP production in bacterial cells.

Published
2019
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4. The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome

Author

Linda Dowd, Theresa Feltwell, Tracey Chillingworth, Stephen Baker, Zahra Hance, Brendan W. Wren, Richard A. Stabler, Nicholas R. Thomson, S. Holroyd, Anne Wright, Audrey Fraser, Sarah Sharp, Adam P. Roberts, Karen Brooks, Michael A. Quail, K. Stevens, Kay Jagels, Peter Mullany, Louise Unwin, Paul Davis, Hongmei Wang, Claire Price, Bart Barrell, Carol Churcher, Ann Cronin, Matthew T. G. Holden, Ana Cerdeño-Tárraga, Nathalie Bason, Neil F. Fairweather, Karen Mungall, Mark Simmonds, Nigel P. Minton, Julian Parkhill, Ester Rabbinowitsch, Sally Whithead, Gordon Dougan, Bruno Dupuy, Mohammed Sebaihia, Sharon Moule, The Wellcome Trust Sanger Institute [Cambridge], Department of Infectious and Tropical Diseases (LSHTM), London School of Hygiene and Tropical Medicine (LSHTM), Eastman Dental Institute [UCL, London], University College of London [London] (UCL), MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Centre for Biomolecular Sciences [Nottingham, UK] (CBS), University of Nottingham, UK (UON), Génétique Moléculaire Bactérienne, Institut Pasteur [Paris] (IP), This work was supported by the Wellcome Trust., We would like to acknowledge the support of the Wellcome Trust Sanger Institute core sequencing and informatics groups. We thank D. Gerding and G. Songer for provision of C. difficile strains, F. Barbut and J. Emerson for help with the antibiotic susceptibility tests, and the BUGs microarray facility at St. George's Hospital for provision of the C. difficile 630 microarray., and Institut Pasteur [Paris]

Subjects
[SDV]Life Sciences [q-bio], MESH: Base Sequence, MESH: Genome, Bacterial, Genome, Drug Resistance, Multiple, Bacterial, MESH: Clostridium difficile/pathogenicity, MESH: Clostridium difficile/physiology, MESH: Spores, Bacterial/physiology, Enterocolitis, Pseudomembranous, MESH: Gastrointestinal Tract/microbiology, Oligonucleotide Array Sequence Analysis, Spores, Bacterial, Genetics, 0303 health sciences, Virulence, Mosaicism, Clostridium difficile, MESH: Enterocolitis, Pseudomembranous/etiology, Adaptation, Physiological, Conjugation, Genetic, MESH: Mosaicism, DNA, Bacterial, Transposable element, Molecular Sequence Data, Biology, MESH: Bacterial Proteins/genetics, MESH: Clostridium difficile/drug effects, MESH: Enterocolitis, Pseudomembranous/microbiology, MESH: DNA Transposable Elements/genetics, 03 medical and health sciences, Bacterial Proteins, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Virulence/genetics, MESH: Drug Resistance, Multiple, Bacterial/genetics, Gene, 030304 developmental biology, Whole genome sequencing, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Clostridioides difficile, 030306 microbiology, Microarray analysis techniques, MESH: Conjugation, Genetic, MESH: Adaptation, Physiological, MESH: DNA, Bacterial/genetics, Gastrointestinal Tract, MESH: Oligonucleotide Array Sequence Analysis, DNA Transposable Elements, Mobile genetic elements, MESH: Clostridium difficile/genetics, Genome, Bacterial
Abstract

International audience; We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism.

Published
2006
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5. The Assembly Mode of the Pseudopilus: a hallmark to distinguish a novel secretion system subtype

Author

Durand, Eric, Alphonse, Sébastien, Brochier-Armanet, Céline, Ball, Geneviève, Douzi, Badreddine, Filloux, Alain, Bernard, Cédric, Voulhoux, Romé, Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Architecture et fonction des Macromolécules Biologiques - UMR 6098 (AFMB), Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1, Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS)

Subjects
Bacterial Proteins/genetics/metabolism, Gene Transfer, Horizontal, Horizontal/*physiology, Bacterial/genetics/metabolism, [SDV]Life Sciences [q-bio], Gene Transfer, Molecular, Pseudomonas aeruginosa/genetics/metabolism, Microbiology, Evolution, Molecular, Fimbriae, Evolution, Bacterial Proteins, Fimbriae, Bacterial, Pseudomonas aeruginosa, Bacterial Secretion Systems, Bacterial Secretion Systems/*physiology
Abstract

International audience; In gram-negative bacteria, type II secretion systems assemble a piston-like structure, called pseudopilus, which expels exoproteins out of the cell. The pseudopilus is constituted by a major pseudopilin that when overproduced multimerizes into a long cell surface structure named hyper-pseudopilus. Pseudomonas aeruginosa possesses two type II secretion systems, Xcp and Hxc. Although major pseudopilins are exchangeable among type II secretion systems, we show that XcpT and HxcT are not. We demonstrate that HxcT does not form a hyper-pseudopilus and is different in amino acid sequence and multimerization properties. Using structure-based mutagenesis, we observe that five mutations are sufficient to revert HxcT into a functional XcpT-like protein, which also becomes capable of forming a hyper-pseudopilus. Phylogenetic and experimental analysis showed that the whole Hxc system was acquired by P. aeruginosa PAO1 and other Pseudomonas species through horizontal gene transfer. We thus identified a new type II secretion subfamily, of which the P. aeruginosa Hxc system is the archetype. This finding demonstrates how similar bacterial machineries evolve toward distinct mechanisms that may contribute specific functions.

Published
2011
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6. Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment

Author

Olivia Alder, Laura P. O'Neill, Ana Pombo, Fabrice Lavial, Philippe Arnaud, Véronique Azuara, Anne Helness, Anil Chandrashekran, Sandra Pinho, Emily Brookes, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Focas Research Institute, Dublin Institute of Technology, Hammersmith Hospital NHS Imperial College Healthcare, MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), University of Birmingham [Birmingham], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)

Subjects
Mouse, Bivalent chromatin, Ubiquitin-Protein Ligases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Early development, Stem cells, Biology, Models, Biological, Histone methylation, 03 medical and health sciences, Mice, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Polycomb-group proteins, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cell Lineage, Gene Silencing, Hox gene, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, Polycomb Repressive Complex 1, 0303 health sciences, Silencing, Gene Expression Profiling, Gene Expression Regulation, Developmental, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Development and Stem Cells, Methyltransferases, DNA Methylation, Embryonic stem cell, Chromatin, Trophoblasts, Repressor Proteins, Blastocyst, DNA methylation, embryonic structures, RNA Interference, RNA Polymerase II, Stem cell, 030217 neurology & neurosurgery, Developmental Biology
Abstract

International audience; Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, thetrophectoderm. We show that a set of somatic lineage regulators (including Hox, Gata and Sox factors) that carry bivalent chromatin enriched in H3K27me3 and H3K4me2 are selectively targeted by Suv39h1-mediated H3K9me3 and de novo DNA methylation in extra-embryonic versus embryonic (pluripotent) lineages, as assessed both in blastocyst-derived stem cells and invivo. This stably repressed state is linked with a loss of gene priming for transcription through the exclusion of PRC1 (Ring1B) and RNA polymerase II complexes at bivalent, lineage-inappropriate genes upon trophoblast lineage commitment. Collectively, our results suggest a mutually exclusive role for Ring1B and Suv39h1 in regulating distinct chromatin states at key developmental genes and propose a novel mechanism by which lineage specification can be reinforced during early development.

Published
2010
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7. Modulation of Shigella virulence in response to available oxygen in vivo

Author

Philippe J. Sansonetti, Nicholas P. West, J. A. Cole, Douglas F. Browning, Marie-Christine Prévost, Christoph M. Tang, Fredrik Palm, Joëlle Mounier, Benoit S. Marteyn, Jonathan G. Shaw, MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, School of Biosciences, University of Birmingham [Birmingham], Division of Genomic Medicine, University of Sheffield Medical School, Department of Medical Cell Biology, Uppsala University, Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Microscopie électronique (Plate-forme), Institut Pasteur [Paris], Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), FRM, Royal Society, ERC, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), and Collège de France - Chaire Microbiologie et Maladies infectieuses

Subjects
Cell signaling, Virulence, Biology, medicine.disease_cause, Shigella flexneri, Type three secretion system, Microbiology, Mice, 03 medical and health sciences, Fumarates, medicine, Animals, Humans, Shigella, Secretion, Anaerobiosis, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Gastrointestinal tract, Nitrates, Multidisciplinary, 030306 microbiology, Effector, Epithelial Cells, Gene Expression Regulation, Bacterial, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, Gastrointestinal Tract, Oxygen, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Host-Pathogen Interactions, bacteria, Rabbits, Oxidation-Reduction, HeLa Cells
Abstract

International audience; Bacteria coordinate expression of virulence determinants in response to localized microenvironments in their hosts. Here we show that Shigella flexneri, which causes dysentery, encounters varying oxygen concentrations in the gastrointestinal tract, which govern activity of its type three secretion system (T3SS). The T3SS is essential for cell invasion and virulence. In anaerobic environments (for example, the gastrointestinal tract lumen), Shigella is primed for invasion and expresses extended T3SS needles while reducing Ipa (invasion plasmid antigen) effector secretion. This is mediated by FNR (fumarate and nitrate reduction), a regulator of anaerobic metabolism that represses transcription of spa32 and spa33, virulence genes that regulate secretion through the T3SS. We demonstrate there is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi. This would reverse the anaerobic block of Ipa secretion, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.

Published
2010
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8. Identification of Biofilm-Associated Cluster (bac) in Pseudomonas aeruginosa Involved in Biofilm Formation and Virulence

Author

Alain Filloux, Camille Macé, Damien Seyer, Thierry Jouenne, Patrick Di-Martino, Virginie Molle, Chanez Chemani, Benoit Guery, Marc Fontaine, Guy-Alain Junter, Pascal Cosette, Polymères Biopolymères Surfaces (PBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche sur les relations matrice extracellulaire-cellules (ERRMECe), Fédération INSTITUT DES MATÉRIAUX DE CERGY-PONTOISE (I-MAT), Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Université Lille 2 - Faculté de Médecine, Biologie et physiologie des états septiques, IFR114-Université de Lille, Droit et Santé, MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut de biologie et chimie des protéines [Lyon] (IBCP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, The French Cystic Fibrosis Foundation (VLM), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and MOLLE, Virginie

Subjects
Male, Mutant, Outer membrane proteins, medicine.disease_cause, Bacterial Adhesion, Infectious Diseases/Bacterial Infections, Mice, Biochemistry/Protein Chemistry, Opportunistic infections, Phage shock, 0303 health sciences, Mice, Inbred BALB C, Multidisciplinary, Virulence, Microbiology/Immunity to Infections, Multidisciplinary Sciences, Multigene Family, Pseudomonas aeruginosa, Medicine, Science & Technology - Other Topics, Biological Assay, Microbiology/Cellular Microbiology and Pathogenesis, Research Article, Surface Properties, General Science & Technology, Science, Hypothetical protein, Molecular Sequence Data, Locus (genetics), Biology, Microbiology, 03 medical and health sciences, Bacterial Proteins, Osmotic Pressure, Cell Line, Tumor, MD Multidisciplinary, medicine, Animals, Humans, Pseudomonas Infections, Amino Acid Sequence, Mutant strains, Vascular permeability, Gene, DNA sequence analysis, 030304 developmental biology, Science & Technology, 030306 microbiology, Biofilm, Computational Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Kinetics, Bacterial biofilms, Protein structure prediction, Genes, Bacterial, Biofilms, Mutation, Glycolipids, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Heat-Shock Response
Abstract

International audience; Biofilms are prevalent in diseases caused by Pseudomonas aeruginosa, an opportunistic and nosocomial pathogen. By a proteomic approach, we previously identified a hypothetical protein of P. aeruginosa (coded by the gene pA3731) that was accumulated by biofilm cells. We report here that a DpA3731 mutant is highly biofilm-defective as compared with the wild-type strain. Using a mouse model of lung infection, we show that the mutation also induces a defect in bacterial growth during the acute phase of infection and an attenuation of the virulence. The pA3731 gene is found to control positively the ability to swarm and to produce extracellular rhamnolipids, and belongs to a cluster of 4 genes (pA3729-pA3732) not previously described in P. aeruginosa. Though the protein PA3731 has a predicted secondary structure similar to that of the Phage Shock Protein, some obvious differences are observed compared to already described psp systems, e.g., this unknown cluster is monocistronic and no homology is found between the other proteins constituting this locus and psp proteins. As E. coli PspA, the amount of the protein PA3731 is enlarged by an osmotic shock, however, not affected by a heat shock. We consequently named this locus bac for biofilm-associated cluster.

Published
2008
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9. Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity

Author

Sylvain Pitarque, Jean-Louis Herrmann, Douglas B. Young, Olivier Schwartz, Germain Puzo, Jérôme Nigou, Philippe H. Lagrange, Mary Jackson, Olivier Neyrolles, François Lecointe, Bruno Payré, Brigitte Gicquel, Graham R. Stewart, Jean-Luc Duteyrat, Gilles Marchal, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de microbiologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et epidémiologie moléculaire des infections microbiennes (EA_3510), Université Paris Diderot - Paris 7 (UPD7), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris], MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This research project was co-financed by the European Commission, within the Sixth Framework Programme (contract no. LSHP-CT-2003-503367), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Génétique mycobactérienne, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Tuberculosis, mycobacteria, dendritic cell, [SDV]Life Sciences [q-bio], dendritic-cell-specific intercellular molecule-3-grabbing non-integrin (DC-SIGN), Receptors, Cell Surface, Biology, Biochemistry, Bacterial Adhesion, Microbiology, Substrate Specificity, Mycobacterium tuberculosis, 03 medical and health sciences, Immune system, Antigen, Species Specificity, medicine, Humans, Lectins, C-Type, Molecular Biology, 030304 developmental biology, 0303 health sciences, Lipoarabinomannan, Lipomannan, 030302 biochemistry & molecular biology, Cell Biology, Dendritic cell, medicine.disease, biology.organism_classification, 3. Good health, DC-SIGN, tuberculosis, biology.protein, lipoarabinomannan, Cell Adhesion Molecules, HeLa Cells, Protein Binding, Research Article
Abstract

International audience; Interactions between dendritic cells and Mycobacterium tuberculosis, the aetiological agent of tuberculosis in humans, are thought to be central to anti-mycobacterial immunity. We have previously shown that M. tuberculosis binds to human monocyte-derived dendritic cells mostly through the C-type lectin DC-SIGN (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209, and we have suggested that DC-SIGN may discriminate between mycobacterial species through recognition of the mannose-capping residues on the lipoglycan lipoarabinomannan of the bacterial envelope. Here, using a variety of fast- and slow-growing Mycobacterium species, we provide further evidence that mycobacteria recognition by DC-SIGN may be restricted to species of the M. tuberculosis complex. Fine analyses of the lipoarabinomannan molecules purified from these species show that the structure and amount of these molecules alone cannot account for such a preferential recognition. We propose that M. tuberculosis recognition by DC-SIGN relies on both a potential difference of accessibility of lipoarabinomannan in its envelope and, more probably, on the binding of additional ligands, possibly including lipomannan, mannose-capped arabinomannan, as well as the mannosylated 19 kDa and 45 kDa [Apa (alanine/proline-rich antigen)] glycoproteins. Altogether, our results reveal that the molecular basis of M. tuberculosis binding to DC-SIGN is more complicated than previously thought and provides further insight into the mechanisms of M. tuberculosis recognition by the immune system.

Published
2005
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10. Revised nomenclature of Clostridium difficile toxins and associated genes

Author

Stuart Johnson, Monica Thelestam, M R Popoff, Christoph von Eichel-Streiber, Abraham L. Sonenshein, Julian I. Rood, Neil F. Fairweather, Ingo Just, Bruno Dupuy, Brendan W. Wren, Dale N. Gerding, Tracy D. Wilkins, David M. Lyerly, Maja Rupnik, University of Ljubljana, Génétique Moléculaire Bactérienne, Institut Pasteur [Paris], MRC Centre for Molecular Microbiology and Infection [Imperial College, London] (CMBI), Imperial College London, Hines VA Medical Center [USA], Loyola University Medical Center (LUMC), Institut für Toxikologie - Institut for Toxicology [Hannover, Germany], Hannover Medical School [Hannover] (MHH)-Medizinische Hochschule Hannover (MHH), TechLab Inc, Toxines bactériennes - Bacterial Toxins, Department of Microbiology [Monash University, Australia], School of Biomedical Sciences [Monash University, Clayton], Monash University [Clayton]-Monash University [Clayton], Department of Molecular Biology and Microbiology [Tufts, Boston], Tufts University School of Medicine [Boston], Department of Microbiology Tumor and Cell Biology [Stockholm], Karolinska Institutet [Stockholm], London School of Hygiene and Tropical Medicine (LSHTM), Johannes Gutenberg - Universität Mainz (JGU), Institut Pasteur [Paris] (IP), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)

Subjects
Microbiology (medical), [SDV]Life Sciences [q-bio], Bacterial Toxins, Clostridium sordellii, MESH: Terminology as Topic, medicine.disease_cause, MESH: Bacterial Proteins/genetics, Microbiology, MESH: Enterotoxins/genetics, Enterotoxins, 03 medical and health sciences, Bacterial Proteins, Terminology as Topic, medicine, Clostridiaceae, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Bacterial Toxins/isolation & purification, Nomenclature, Gene, 030304 developmental biology, 0303 health sciences, biology, Clostridioides difficile, 030306 microbiology, Toxin, Clostridiales, General Medicine, Clostridium difficile, Clostridium novyi, biology.organism_classification, MESH: Clostridium difficile/genetics, MESH: Bacterial Toxins/genetics
Abstract

This paper was presented at the round-table discussion on Clostridium difficile nomenclature at the First International Clostridium difficile Symposium, Kranjska Gora, Slovenia, 5–7 May 2004.; International audience; Several different nomenclatures have been applied to the Clostridium difficile toxins and their associated genes. This paper summarizes the new nomenclature that has been agreed to by the research groups currently active in the field. The revised nomenclature includes C. difficile toxins and other related large clostridial toxins produced by Clostridium sordellii and Clostridium novyi, and corresponding toxin genes, as well as toxin production types of C. difficile strains.

Published
2005
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