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1. Fluorescent secreted bacterial effectors reveal active intravacuolar proliferation of Listeria monocytogenes in epithelial cells

Author: Peron Cane, Caroline, Carlos Fernandez, José, Leblanc, Julien, Wingertsmann, Laure, Gautier, Arnaud, Desprat, Nicolas, Lebreton, Alice, Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de physique de l'ENS - ENS Paris (LPENS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - 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), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Université Paris Diderot - Paris 7 (UPD7), ABCD : Biophysique des Biomolécules, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), ATIP-Avenir, Amorçage de jeune équipe de la Fondation pour la Recherche Médicale (FRM-AJE20131128944), Programme Émergences – Recherche médicale de la Mairie de Paris, ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Chimie Moléculaire de Paris Centre (FR 2769), 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), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Lebreton, Alice, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), 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)-École normale supérieure - Paris (ENS Paris), Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris)
Subjects: Physiology, Secretion Systems, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Pathology and Laboratory Medicine, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Epithelium, Hemolysin Proteins, Cytosol, Bacterial secretion, Animal Cells, Phagosomes, Microbial Physiology, Medicine and Health Sciences, Listeriosis, Intravacuolar life, Bacterial Physiology, Biology (General), Heat-Shock Proteins, Virulence factors, Bacterial Pathogens, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Intracellular Pathogens, Medical Microbiology, Cellular Structures and Organelles, Pathogens, Cellular Types, Anatomy, Research Article, Listeria, Imaging Techniques, QH301-705.5, Bacterial Toxins, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Research and Analysis Methods, Microbiology, Cell Line, Bacterial Proteins, Fluorescence Imaging, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, Live cell imaging, Microbial Pathogens, Secretion, Cell Proliferation, Fluorescent Dyes, Bacteria, Host-pathogen interactions, Macrophages, Organisms, Biology and Life Sciences, Epithelial Cells, Bacteriology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, RC581-607, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biological Tissue, Vacuoles, Pore-forming toxin, Caco-2 Cells, Immunologic diseases. Allergy, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Physiological Processes
Abstract: Real-time imaging of bacterial virulence factor dynamics is hampered by the limited number of fluorescent tools suitable for tagging secreted effectors. Here, we demonstrated that the fluorogenic reporter FAST could be used to tag secreted proteins, and we implemented it to monitor infection dynamics in epithelial cells exposed to the human pathogen Listeria monocytogenes (Lm). By tracking individual FAST-labelled vacuoles after Lm internalisation into cells, we unveiled the heterogeneity of residence time inside entry vacuoles. Although half of the bacterial population escaped within 13 minutes after entry, 12% of bacteria remained entrapped over an hour inside long term vacuoles, and sometimes much longer, regardless of the secretion of the pore-forming toxin listeriolysin O (LLO). We imaged LLO-FAST in these long-term vacuoles, and showed that LLO enabled Lm to proliferate inside these compartments, reminiscent of what had been previously observed for Spacious Listeria-containing phagosomes (SLAPs). Unexpectedly, inside epithelial SLAP-like vacuoles (eSLAPs), Lm proliferated as fast as in the host cytosol. eSLAPs thus constitute an alternative replication niche in epithelial cells that might promote the colonization of host tissues., Author summary Bacterial pathogens secrete virulence factors to subvert their hosts; however, monitoring bacterial secretion in real-time remains challenging. Here, we developed a convenient method that enabled fluorescent imaging of secreted proteins in live microscopy, and applied it to the human pathogen Listeria monocytogenes. Listeria has been described to invade cells and proliferate in their cytosol; it is first internalized inside vacuoles, from where it escapes thanks to the secretion of virulence factors that disrupt membranes. Our work revealed the existence, in human epithelial cells, of a population of Listeria that failed to escape vacuoles but instead multiplied efficiently therein, despite—and in fact, thanks to—the active secretion of a toxin that permeates membranes. This intravacuolar niche may provide Listeria with an alternative strategy to colonize its host.
Published: 2020

2. An alternative replication niche for Listeria monocytogenes revealed by fluorescent tagging of bacterial secreted effectors

Author: Peron Cane, Caroline, Leblanc, Julien, Wingertsmann, Laure, Fernandez, José-Carlos, Gautier, Arnaud, Desprat, Nicolas, and Lebreton, Alice
Abstract: Tracking the dynamics of secreted virulence factors in real time is impaired by the paucity of appropriate fluorescent tools. Here, we took advantage of the fluorogenic reporter FAST to tag secreted proteins and monitor infection dynamics among a population of epithelial cells infected by Listeria monocytogenes ( Lm ). Thereby, we unveiled the heterogeneity of Lm residence time in internalisation vacuoles. Although half of the bacterial population escaped rapidly, a significant fraction remained entrapped several hours in Long Residence Vacuoles (LRVs), independently of the secretion of the pore-forming toxin listeriolysin O (LLO). Unexpectedly, LLO enabled Lm to proliferate inside these compartments as fast as in the cytosol. LRVs display similarities with the spacious Listeria -containing phagosomes described in macrophages, and could constitute an alternative replication niche for Lm in epithelial cells.
Published: 2019
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3. Listeriolysin O promotes the intravacuolar growth of Listeria monocytogenes in epithelial cells

Author: Peron Cane, Caroline, Leblanc, Julien, Wingertsmann, Laure, Carlos Fernandez, José, Gautier, Arnaud, Desprat, Nicolas, Lebreton, Alice, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ABCD : Biophysique des Biomolécules, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Université Paris Diderot - Paris 7 (UPD7)-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)-Sorbonne Université (SU)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire des biomolécules (LBM UMR 7203), Institut National de la Santé et de la Recherche Médicale (INSERM)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Université Paris Diderot - Paris 7 (UPD7), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ATIP-Avenir, Amorçage de jeune équipe de la Fondation pour la Recherche Médicale (FRM-AJE20131128944), Programme Émergences – Recherche médicale de la Mairie de Paris, ANR-10-IDEX-0001-02/10-LABX-0054,MEMOLIFE,Memory in living systems: an integrated approach(2010), ANR-10-IDEX-0001-02/10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire de Paris Centre (FR 2769), Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-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), and 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
Subjects: [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Bacterial secretion, Virulence factors, Host-pathogen interactions, Intravacuolar life, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pore-forming toxin, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Live cell imaging, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Published: 2019

4. Régulations post-transcriptionnelles de l'expression génique de la cellule hôte en réponse à l'infection bactérienne

Author: Lebreton, Alice, Institut National de la Recherche Agronomique (INRA), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (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)-École normale supérieure - Paris (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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot (Paris 7), Jonathan Weitzman, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lebreton, Alice, Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, and 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)
Subjects: Translation, Host-pathogen interactions, Virulence factors, Interactions hôte-pathogène, [SDV]Life Sciences [q-bio], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Facteurs de virulence, Expression génique, [SDV] Life Sciences [q-bio], Traduction, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Post-transcriptional regulations, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Régulations post-transcriptionnelles, Gene expression, mRNA stability, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Stabilité des ARN
Abstract: Listeria monocytogenes est un pathogène fréquent du bétail et l’agent de la listériose humaine, une maladie grave pour les femmes enceintes, les personnes âgées ou immunodéprimées. La prolifération de cette bactérie dans les cellules qu’elle infecte s’accompagne d’une reprogrammation de l’expression génique et des fonctions cellulaires.Après un doctorat sous la direction de Micheline Fromont-Racine (groupe d’Alain Jacquier) à l’Institut Pasteur sur la biogenèse des ribosomes, mes travaux de post-doctorat dans le groupe dirigé par Bertrand Séraphin au Centre de Génétique Moléculaire (Gif-sur-Yvette) ont mis en évidence une nouvelle activité enzymatique – une endonucléase – dans l’un des complexes de dégradation des ARN eucaryotes les plus étudiés, l’exosome.Recrutée à l’INRA en tant que chargée de recherche en 2008, j’ai rejoint jusqu’en 2014 l’équipe dirigée par Pascale Cossart à l’Institut Pasteur. J’y ai étudié comment la bactérie pathogène Listeria monocytogenes détourne la machinerie de répression chromatinienne des cellules qu’elle infecte, pour moduler certaines réponses immunitaires.Je dirige depuis octobre 2014 à l’Institut de Biologie de l’École Normale Supérieure (IBENS) une équipe de recherche qui étudie les mécanismes post-transcriptionnels régulant les ARNm eucaryotes en réponse à l’infection par Listeria monocytogenes. Nous travaillons sur quatre problématiques principales : L’infection conduit-elle à une dégradation globale ou spécifique des ARNm ? La machinerie et l’efficacité de la traduction sont-elles perturbées ? Quels effecteurs moléculaires de la bactérie ou de l’hôte sont impliqués dans ces processus ? Quelles en sont les conséquences patho-physiologiques ?Ces travaux, reposant sur des technologies haut débit adaptées à l’étude du devenir des ARNm, ainsi que sur des approches plus classiques de microbiologie cellulaire, permettront de mieux comprendre les impératifs de l’adaptation mutuelle entre la bactérie et son hôte, d’identifier de nouveaux facteurs de virulence, et d’explorer les voies de contrôle traductionnel eucaryotes dans un contexte d’infection.
Published: 2015

5. Dynamics of pre-ribosomal factors along the large ribosomal subunit biogenesis in S. cerevisiae

Author: Lebreton, Alice, Génétique des Interactions Macromoléculaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris-Diderot - Paris VII, Micheline Fromont-Racine, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: transport nucléo-cytoplasmique, [SDV.GEN]Life Sciences [q-bio]/Genetics, ribosome biogenesis, pre-ribosomal factor, assembly order, [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], Saccharomyces cerevisiae, facteur pré-ribosomique, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], facteur navette, SILAC, shuttling factor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ordre d'assemblage, biogenèse des ribosomes, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ribosomal RNA, nucleo-cytoplasmic transport, ARN ribosomique
Abstract: This work focuses on the dynamics of assembly, dissociation and recycling of proteins involved in the biogenesis of the large ribosomal subunit in Saccharomyces cerevisiae. It sheds some light on two control points in this metabolic pathway, localised in the nucleus and the cytoplasm respectively.We have shown that the nuclear protein Nsa2, which is very conserved throughout the eukaryotic kingdom, is required for the correct maturation of the 27SB ribosomal RNA precursor. Nsa2 is an unstable factor, regulated in correlation with the activity of ribosome biogenesis; it thus constitutes a good candidate for the integration of various signals resulting in the regulation of this metabolic pathway. Besides, using the SILAC technique, we could define groups of early or late acting factors relative to the Nsa2 action time.In the cytoplasm, we identified a protein network, which marks the end of ribosome biogenesis and triggers the entry of new ribosomal subunits into translation. The cytoplasmic protein Rei1 and the karyopherin Kap121 are both required for the recycling from the cytoplasm to the nucleus of a dimer of shuttling factors, Arx1-Alb1. This recycling enables the dissociation of the anti-association factor Tif6 from the large ribosomal subunit, which can consequently bind the small ribosomal subunit and enter translation.; Les travaux de ce mémoire portent sur la dynamique d'assemblage, de dissociation et de recyclage des protéines impliquées dans la biogenèse de la grande sous-unité ribosomique chez la levure Saccharomyces cerevisiae. Ils permettent une meilleure compréhension de deux points de contrôle de cette voie métabolique, l'un dans le noyau, l'autre dans le cytoplasme. Nous avons montré que la protéine nucléaire Nsa2, extrêmement conservée chez les Eucaryotes, est requise pour la maturation correcte de l'intermédiaire d'ARN ribosomique 27SB. Nsa2 est un facteur instable et régulé en fonction de l'activité de la biogenèse des ribosomes ; à ce titre, il pourrait centraliser différents signaux de contrôle de la voie métabolique. Par ailleurs, la technique de SILAC nous a permis de définir des groupes de facteurs pré-ribosomiques précoces ou tardifs par rapport au point d'action de Nsa2.Dans le cytoplasme, nous avons mis en évidence un réseau de protéines marquant la transition entre la fin de la biogenèse de la grande sous-unité et l'initiation de la traduction. La protéine cytoplasmique Rei1 et la karyophérine Kap121 sont requises pour le recyclage du dimère de facteurs navettes Arx1-Alb1, du cytoplasme vers le noyau. Ce recyclage conditionne la dissociation entre le facteur d'anti-association Tif6 et la grande sous-unité ribosomique, qui peut dès lors se lier à la petite sous-unité ribosomique et participer à la traduction.
Published: 2006

6. Dynamics of pre-ribosomal factors along the large ribosomal subunit biogenesis in S. cerevisiae

Author: Lebreton, Alice, Génétique des Interactions Macromoléculaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris-Diderot - Paris VII, and Micheline Fromont-Racine
Subjects: transport nucléo-cytoplasmique, SDV:BC, [SDV.GEN]Life Sciences [q-bio]/Genetics, SDV:BBM:BC, ribosome biogenesis, pre-ribosomal factor, assembly order, [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], Saccharomyces cerevisiae, ribosomal RNA, shuttling factor, nucleo-cytoplasmic transport, SILAC, facteur pré-ribosomique, facteur navette, ARN ribosomique, biogenèse des ribosomes, ordre d'assemblage, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], facteur navette, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ARN ribosomique
Abstract: This work focuses on the dynamics of assembly, dissociation and recycling of proteins involved in the biogenesis of the large ribosomal subunit in Saccharomyces cerevisiae. It sheds some light on two control points in this metabolic pathway, localised in the nucleus and the cytoplasm respectively.We have shown that the nuclear protein Nsa2, which is very conserved throughout the eukaryotic kingdom, is required for the correct maturation of the 27SB ribosomal RNA precursor. Nsa2 is an unstable factor, regulated in correlation with the activity of ribosome biogenesis; it thus constitutes a good candidate for the integration of various signals resulting in the regulation of this metabolic pathway. Besides, using the SILAC technique, we could define groups of early or late acting factors relative to the Nsa2 action time.In the cytoplasm, we identified a protein network, which marks the end of ribosome biogenesis and triggers the entry of new ribosomal subunits into translation. The cytoplasmic protein Rei1 and the karyopherin Kap121 are both required for the recycling from the cytoplasm to the nucleus of a dimer of shuttling factors, Arx1-Alb1. This recycling enables the dissociation of the anti-association factor Tif6 from the large ribosomal subunit, which can consequently bind the small ribosomal subunit and enter translation., Les travaux de ce mémoire portent sur la dynamique d'assemblage, de dissociation et de recyclage des protéines impliquées dans la biogenèse de la grande sous-unité ribosomique chez la levure Saccharomyces cerevisiae. Ils permettent une meilleure compréhension de deux points de contrôle de cette voie métabolique, l'un dans le noyau, l'autre dans le cytoplasme. Nous avons montré que la protéine nucléaire Nsa2, extrêmement conservée chez les Eucaryotes, est requise pour la maturation correcte de l'intermédiaire d'ARN ribosomique 27SB. Nsa2 est un facteur instable et régulé en fonction de l'activité de la biogenèse des ribosomes ; à ce titre, il pourrait centraliser différents signaux de contrôle de la voie métabolique. Par ailleurs, la technique de SILAC nous a permis de définir des groupes de facteurs pré-ribosomiques précoces ou tardifs par rapport au point d'action de Nsa2.Dans le cytoplasme, nous avons mis en évidence un réseau de protéines marquant la transition entre la fin de la biogenèse de la grande sous-unité et l'initiation de la traduction. La protéine cytoplasmique Rei1 et la karyophérine Kap121 sont requises pour le recyclage du dimère de facteurs navettes Arx1-Alb1, du cytoplasme vers le noyau. Ce recyclage conditionne la dissociation entre le facteur d'anti-association Tif6 et la grande sous-unité ribosomique, qui peut dès lors se lier à la petite sous-unité ribosomique et participer à la traduction.
Published: 2006

7. Adaptations of intracellular bacteria to vacuolar or cytosolic niches

Author: Thomas Petit, Alice Lebreton, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), 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)-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), Programme Émergence(s) Recherche médicale de la mairie de Paris, ANR-20-CE15-0030,LiVaLife,Dynamique et contribution à l'infection des vies intravacuolaires de Listeria(2020), Lebreton, Alice, and Dynamique et contribution à l'infection des vies intravacuolaires de Listeria - - LiVaLife2020 - ANR-20-CE15-0030 - AAPG2020 - VALID
Subjects: Salmonella typhimurium, Microbiology (medical), vacuole, invasive bacteria, pathogenic bacteria, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Listeria monocytogenes, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infectious Diseases, intracellular lifestyle, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Host-Pathogen Interactions, Vacuoles, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, cytosol, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Invasive bacteria colonise their host tissues by establishing niches inside eukaryotic cells, where they grow either in the cytosol or inside a specialised vacuole. These two distinct intracellular lifestyles both present benefits but also impose various constraints on pathogenic microorganisms, in terms of nutrient acquisition, space requirements, exposure to immune responses, and ability to disseminate. Here we review the major characteristics of cytosolic and vacuolar lifestyles and the strategies used by bacteria to overcome challenges specific to each compartment. Recent research providing evidence that these scenarios are not mutually exclusive is presented, with the dual lifestyles of two foodborne pathogens, Listeria monocytogenes and Salmonella Typhimurium, discussed in detail. Finally, we elaborate on the conceptual implications of polyvalence from the perspective of host-pathogen interactions.
Published: 2022

8. Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism

Author: Slimane Ait-Si-Ali, Marie Wattenhofer-Donzé, Marie-France Champy, Renaud Pourpre, Alice Lebreton, Goran Lakisic, Pascale Cossart, Morwenna Le Guillou, Hélène Bierne, Tania Sorg, Guillaume Soubigou, Emanuele Libertini, Anne C. Ferguson-Smith, Jean Feunteun, Jean-Yves Coppée, Elizabeth J. Radford, Olivia Wendling, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Clinique de la Souris (ICS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris] (IP), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, French Ligue Nationale Contre le Cancer (comité régional d’Ile–de-France, LNCC RS10/75–76 and LNCC 131/12, INRA AO blanc MICA 2011, iXcore Fundation for Research, ANR-11-BSV3-0003,EPILIS,Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes(2011), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Lebreton, Alice, BLANC - Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes - - EPILIS2011 - ANR-11-BSV3-0003 - BLANC - VALID, Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID, Bierne, Hélène, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Radford, Elizabeth [0000-0002-8336-6045], Ferguson-Smith, Anne [0000-0003-4996-9990], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Embryology, Cancer Research, Chromosomal Proteins, Non-Histone, Placenta, dna methylation, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biochemistry, Mice, Pregnancy, Gene expression, Medicine and Health Sciences, Small interfering RNAs, Genetics (clinical), estrogen-receptor-alpha, histone deacetylase, transcriptional repression, glycogen cells, breast-cancer, sant domain, Regulation of gene expression, Mice, Knockout, biology, Chromosome Biology, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Gene Expression Regulation, Developmental, Nuclear Proteins, Genomics, Chromatin, Precipitation Techniques, Cell biology, Nucleic acids, DNA-Binding Proteins, Histone, DNA methylation, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Epigenetics, Female, Steroids, Anatomy, DNA modification, Transcriptome Analysis, Chromatin modification, Research Article, lcsh:QH426-470, Steroid hormone receptor, Research and Analysis Methods, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Genetics, Immunoprecipitation, Animals, Humans, Non-coding RNA, Molecular Biology, Transcription factor, Ecology, Evolution, Behavior and Systematics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Reproductive System, Estrogen Receptor alpha, Biology and Life Sciences, Computational Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, DNA, Genome Analysis, Molecular biology, Placentation, Gene regulation, lcsh:Genetics, 030104 developmental biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, HEK293 Cells, biology.protein, RNA, Transcriptome, Developmental Biology, Transcription Factors
Abstract: BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome data from murine Bahd1 knockout (KO) placentas at stages E16.5 and E18.5 of gestation, Bahd1-KO embryonic fibroblasts, and human cells stably expressing BAHD1, we also show that changes in BAHD1 levels alter expression of steroid/lipid metabolism genes. Biochemical analysis of the BAHD1-associated multiprotein complex identifies MIER proteins as novel partners of BAHD1 and suggests that BAHD1-MIER interaction forms a hub for histone deacetylases and methyltransferases, chromatin readers and transcription factors. We further show that overexpression of BAHD1 leads to an increase of MIER1 enrichment on the inactive X chromosome (Xi). In addition, BAHD1 and MIER1/3 repress expression of the steroid hormone receptor genes ESR1 and PGR, both playing important roles in placental development and energy metabolism. Moreover, modulation of BAHD1 expression in HEK293 cells triggers epigenetic changes at the ESR1 locus. Together, these results identify BAHD1 as a core component of a chromatin-repressive complex regulating placental morphogenesis and body fat storage and suggest that its dysfunction may contribute to several human diseases., Author Summary The importance of epigenetics in regulation and dysfunction of metabolic pathways is increasingly recognized but the underlying mechanisms and molecular actors involved remain incompletely characterized. Here, we provide evidence that the heterochromatinization factor BAHD1 cooperates with MIER proteins to assemble chromatin-repressive complexes that control a network of metabolic genes involved in placental and fetal growth and in cholesterol homeostasis.
Published: 2020
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9. Visualizing the dynamics of exported bacterial proteins with the chemogenetic fluorescent reporter FAST

Author: Alice Lebreton, Yankel Chekli, Dario Dell'Arciprete, Arnaud Gautier, Chenge Li, Jean-François Allemand, Nicolas Desprat, Christophe Beloin, Caroline Peron-Cane, Jean-Marc Ghigo, Génétique des Biofilms - Genetics of Biofilms, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED BioSPC), Université Sorbonne Paris Cité (USPC)-Université de Paris (UP), Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - 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)-École normale supérieure - Paris (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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ABCD : Biophysique des Biomolécules, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - 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), Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Fondation pour la Recherche Médicale FRM-DEQ20180339185, Fondation pour la Recherche Médicale FRM-AJE20131128944, Inserm ATIP-Avenir, Mairie de Paris (programme Émergences – Recherche médicale), Marie Sklodowska-Curie Action MSCA-IF-2018 (ERC), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-19-CE13-0026,ADOBE,Dynamique de l'adhésion au niveau de l'enveloppe bactérienne(2019), European Project: ERC-2016-CoG-724705 ,FLUOSWITCH, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut de biologie de l'ENS Paris (IBENS), 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)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Chimie Moléculaire de Paris Centre (FR 2769), 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), Lebreton, Alice, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Dynamique de l'adhésion au niveau de l'enveloppe bactérienne - - ADOBE2019 - ANR-19-CE13-0026 - AAPG2019 - VALID, Pushing the frontiers of biological imaging with genetically encoded fluorescence switches - FLUOSWITCH - ERC-2016-CoG-724705 - INCOMING, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris)
Subjects: 0301 basic medicine, Science, 030106 microbiology, Cell, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, Article, Bacterial cell structure, 03 medical and health sciences, Bacterial Proteins, Live cell imaging, Escherichia coli, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Bacteria, microcolonies, fluorescent reporters, FAST complex, invasin, bacterial envelope, surface proteins, Secretion, Adhesins, Bacterial, 030304 developmental biology, Intimin, 0303 health sciences, Multidisciplinary, Membranes, biology, 030306 microbiology, Chemistry, Escherichia coli Proteins, Cell Membrane, Bacteriology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell biology, Bacterial adhesin, Luminescent Proteins, 030104 developmental biology, medicine.anatomical_structure, Luminescent Measurements, Genetic engineering, Medicine, Pathogens, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Chemical tools, Microbial genetics, Bacteria
Abstract: Bacterial proteins exported to the cell surface play key cellular functions. However, despite the interest to study the localisation of surface proteins such as adhesins, transporters or hydrolases, monitoring their dynamics in live imaging remains challenging, due to the limited availability of fluorescent probes remaining functional after secretion. In this work, we used the Escherichia coli intimin and the Listeria monocytogenes InlB invasin as surface exposed scaffolds fused with the recently developed chemogenetic fluorescent reporter protein FAST. Using both membrane permeant (HBR-3,5DM) and non-permeant (HBRAA-3E) fluorogens that fluoresce upon binding to FAST, we demonstrated that fully functional FAST can be exposed at the cell surface and used to specifically tag the external side of the bacterial envelop in both diderm and monoderm bacteria. Our work opens new avenues to study the organization and dynamics of the bacterial cell surface proteins.
Published: 2020

10. Coordination of transcriptional and translational regulations in human cells infected by Listeria monocytogenes

Author: Sebastian Rupp, Vinko Besic, Alice Lebreton, Benoît Noël, Fatemeh Habibolahi, Auguste Genovesio, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Fondation pour la Recherche Médicale (FRM-AJE20131128944), Inserm ATIP-Avenir, Mairie de Paris 15(Programme Émergences – Recherche médicale), SNF Early Postdoc Mobility grant P2BEP3_168721, ANR-10-IDEX-0001-02/10-LABX-0054,MEMOLIFE,Memory in living systems: an integrated approach(2010), ANR-10-IDEX-0001-02/10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - 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)-École normale supérieure - Paris (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), Mairie de Paris (Programme Émergences – Recherche médicale), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Lebreton, Alice, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris
Subjects: Translation, 5'-terminal oligopyrimidine motif, 5'-terminal oligopyrimidine, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, PABPC1, Listeria monocytogenes, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Protein biosynthesis, Ribosome profiling, Gene, Psychological repression, 030304 developmental biology, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Host-pathogen interactions, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Poly(A)-binding proteins, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030217 neurology & neurosurgery
Abstract: The invasion of mammalian cells by intracellular bacterial pathogens reshuffles their gene expression and functions; however, we lack dynamic insight into the distinct control levels that shape the host response. Here, we have addressed the respective contribution of transcriptional and translational regulations during a timecourse of infection of human intestinal epithelial cells by an epidemic strain of Listeria monocytogenes, using transcriptome analysis paralleled with ribosome profiling. Upregulations were dominated by early transcriptional activation of pro-inflammatory genes, whereas translation inhibition appeared as the major driver of downregulations. Instead of a widespread but transient shutoff, translation inhibition affected specifically and durably transcripts encoding components of the translation machinery harbouring a 5’-terminal oligopyrimidine motif. Pre-silencing the most repressed target gene (PABPC1) slowed down the intracellular multiplication of Listeria monocytogenes, suggesting that the infected host cell can benefit from the repression of genes involved in protein synthesis and thereby better control infection.
Published: 2019

11. ALFA: annotation landscape for aligned reads

Author: Alice Lebreton, Charles Bernard, Benoît Noël, Leïla Bastianelli, Mathieu Bahin, Auguste Genovesio, Valentine Murigneux, Hervé Le Hir, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Fondation pour la Recherche Médicale (FRM-AJE20131128944), Inserm ATIP-Avenir, Programme Émergences – Recherche médicale (Mairie de Paris), ANR-10-IDEX-0001-02/10-LABX-0054,MEMOLIFE,Memory in living systems: an integrated approach(2010), ANR-10-IDEX-0001-02/10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Lebreton, Alice, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Genovesio, Auguste, École normale supérieure - Paris (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)-École normale supérieure - Paris (ENS Paris), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, and 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)
Subjects: 0106 biological sciences, lcsh:QH426-470, lcsh:Biotechnology, Arabidopsis, transcription, noncoding rna, tool, universal, post mapping, quality control, ngs, Saccharomyces cerevisiae, Computational biology, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 01 natural sciences, Data type, Mice, 03 medical and health sciences, Annotation, lcsh:TP248.13-248.65, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Animals, Humans, Caenorhabditis elegans, 030304 developmental biology, Protein coding, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Sequence Analysis, RNA, Gene Expression Profiling, Computational Biology, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], lcsh:Genetics, Homo sapiens, Data quality, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA microarray, Functional genomics, Software, 010606 plant biology & botany, Biotechnology, Reference genome
Abstract: Background The last 10 years have seen the rise of countless functional genomics studies based on Next-Generation Sequencing (NGS). In the vast majority of cases, whatever the species, whatever the experiment, the two first steps of data analysis consist of a quality control of the raw reads followed by a mapping of those reads to a reference genome/transcriptome. Subsequent steps then depend on the type of study that is being made. While some tools have been proposed for investigating data quality after the mapping step, there is no commonly adopted framework that would be easy to use and broadly applicable to any NGS data type. Results We present ALFA, a simple but universal tool that can be used after the mapping step on any kind of NGS experiment data for any organism with available genomic annotations. In a single command line, ALFA can compute and display distribution of reads by categories (exon, intron, UTR, etc.) and biotypes (protein coding, miRNA, etc.) for a given aligned dataset with nucleotide precision. We present applications of ALFA to Ribo-Seq and RNA-Seq on Homo sapiens, CLIP-Seq on Mus musculus, RNA-Seq on Saccharomyces cerevisiae, Bisulfite sequencing on Arabidopsis thaliana and ChIP-Seq on Caenorhabditis elegans. Conclusions We show that ALFA provides a powerful and broadly applicable approach for post mapping quality control and to produce a global overview using common or dedicated annotations. It is made available to the community as an easy to install command line tool and from the Galaxy Tool Shed.
Published: 2019

12. Coordination of transcriptional and translational regulations in human cells infected by Listeria monocytogenes

Author: Besic, Vinko, Habibolahi, Fatemeh, Noël, Benoît, Rupp, Sebastian, Genovesio, Auguste, and Lebreton, Alice
Subjects: Listeria monocytogenes, Host-pathogen interactions, Translation, 5'-terminal oligopyrimidine (5'-TOP)
Abstract: The invasion of mammalian cells by intracellular bacterial pathogens reshuffles their gene expression and functions; however, we lack dynamic insight into the distinct control levels that shape the host response. By comparing ribosome profiling and transcriptome data, we have addressed the respective contribution of transcriptional and translational regulations during a time-course of infection of human intestinal epithelial cells by an epidemic strain of Listeria monocytogenes. Upregulations were dominated by early transcriptional activation of pro-inflammatory genes, whereas translation inhibition appeared as the major source of downregulations. Instead of a widespread shutoff, translation inhibition affected durably and specifically transcripts encoding components of the translation machinery, and harbouring a 5’-terminal oligopyrimidine motif. Pre-silencing the most repressed target gene (PABPC1) slowed down the intracellular multiplication of Listeria, suggesting that the infected host cell can benefit from the repression of genes involved in protein synthesis and thereby better control infection.
Published: 2019

13. Listeriolysin O promotes the intravacuolar growth of Listeria monocytogenes in epithelial cells

Author: Cane, Caroline Peron, Leblanc, Julien, Wingertsmann, Laure, Fernandez, José Carlos, Gautier, Arnaud, Desprat, Nicolas, and Lebreton, Alice
Published: 2019

14. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression

Author: Alice Lebreton, Pascale Cossart, Institut National de la Recherche Agronomique (INRA), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), FRM-AJE20131128944ATIP-AvenirProgram Émergences – Recherche médicale (Marie de Paris)Fondation le Roch Les Mousquetaires, ANR-10-BINF-0002,BACNET,Exploring composition and dynamics of bacterial regulatory networks(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (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)-École normale supérieure - Paris (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), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), ANR-10-BINF-0201,BACNET,Investissement d'Avenir BACNET, ANR: 10-LABX-62-01,IBEID,ANR, ANR-10-IDEX-0001-02/10-LABX-0054,MEMOLIFE,Memory in living systems: an integrated approach(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Lebreton, Alice, Exploring composition and dynamics of bacterial regulatory networks - - BACNET2010 - ANR-10-BINF-0002 - BINF - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, and Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID
Subjects: 0301 basic medicine, Riboswitch, Untranslated region, RNA, Untranslated, Operon, riboswitch, non-coding RNA, Non-coding RNA, transcriptome, excludon, thermosensor, CRISPR, Review, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, Mice, Bacterial Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, Humans, Clustered Regularly Interspaced Short Palindromic Repeats, Molecular Biology, Regulation of gene expression, Genetics, Virulence, RNA, RNA-Binding Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Gene Expression Regulation, Bacterial, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, RNA, Bacterial, 030104 developmental biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene-Environment Interaction, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Peptide Termination Factors
Abstract: International audience; The model opportunistic pathogen Listeria monocytogenes has been the object of extensive research, aiming at understanding its ability to colonize diverse environmental niches and animal hosts. Bacterial transcriptomes in various conditions reflect this efficient adaptability. We review here our current knowledge of the mechanisms allowing L. monocytogenes to respond to environmental changes and trigger pathogenicity, with a special focus on RNA-mediated control of gene expression. We highlight how these studies have brought novel concepts in prokaryotic gene regulation, such as the 'excludon' where the 5'-UTR of a messenger also acts as an antisense regulator of an operon transcribed in opposite orientation, or the notion that riboswitches can regulate non-coding RNAs to integrate complex metabolic stimuli into regulatory networks. Overall, the Listeria model exemplifies that fine RNA tuners act together with master regulatory proteins to orchestrate appropriate transcriptional programmes.
Published: 2017

15. 1926–2016: 90 Years of listeriology

Author: Alice Lebreton, Fabrizia Stavru, Pascale Cossart, Sylvain Brisse, Institut National de la Recherche Agronomique (INRA), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (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)-École normale supérieure - Paris (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), Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Prévention et Thérapie Moléculaires des Maladies humaines, Institut Pasteur [Paris], Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'école normale supérieure (IBENS), Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - École normale supérieure - Paris (ENS Paris), Institut National de la Recherche Agronomique (INRA) - Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique évolutive des Microbes, Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-62-IBEID, IBEID, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Lebreton, Alice, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Cossart, Pascale
Subjects: 0301 basic medicine, Epidemiology, Cellular microbiology, Immunology, Genomics, Computational biology, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, Listeria monocytogenes, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Listeria spp, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Virulence factors, Biological modeling, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Listeria, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Typing methods, listeria monocytogenes, listeria spp, epidemiology, cellular microbiology, virulence factors, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; ISOPOL – for "International Symposium on Problems of Listeria and Listeriosis" – meetings gather every three years since 1957 participants from all over the world and allow exchange and update on a wide array of topics concerning Listeria and listeriosis, ranging from epidemiology, diagnostic, and typing methods, to genomics, post-genomics, fundamental microbiology, cell biology and pathogenesis. The XIXth ISOPOL meeting took place in Paris from June 14th to 17th, 2016 at Institut Pasteur. We provide here a report of the talks that were given during the meeting, which represents an up-to-date overview of ongoing research on this important pathogen and biological model.
Published: 2016

16. Overexpression of the Heterochromatinization Factor BAHD1 in HEK293 Cells Differentially Reshapes the DNA Methylome on Autosomes and X Chromosome

Author: Emanuele eLibertini, Alice eLebreton, Goran eLakisic, Marie-Agnès eDillies, Stephan eBeck, Jean-Yves eCoppée, Pascale eCossart, Hélène eBierne, Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Medical Genomics Group, University College of London [London] (UCL)-UCL Cancer Institute, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-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, Ligue Nationale Contre le Cancer (comité régional d’Ile-de-France, LNCC RS10/75–76 and LNCC 131/12), Institut National de la Recherche Agronomique (AO blanc 2011, MICA), Wellcome Trust (WT99148), Royal Society Wolfson Research Merit Award (WM100023), ANR-11-BSV3-0003,EPILIS,Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes(2011), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), European Project: 257082,EC:FP7:HEALTH,FP7-HEALTH-2010-two-stage,EPIGENESYS(2010), European Project: 316758,EC:FP7:PEOPLE,FP7-PEOPLE-2012-ITN,EPITRAIN(2013), European Project: 282510,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,BLUEPRINT(2011), Lebreton, Alice, BLANC - Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes - - EPILIS2011 - ANR-11-BSV3-0003 - BLANC - VALID, Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID, Epigenetics towards systems biology - EPIGENESYS - - EC:FP7:HEALTH2010-10-01 - 2016-03-31 - 257082 - VALID, Epigenetic Training Network - Innovative techniques and models to understand epigenetic regulation in the pathogenesis of common diseases - EPITRAIN - - EC:FP7:PEOPLE2013-03-01 - 2017-02-28 - 316758 - VALID, A BLUEPRINT of Haematopoietic Epigenomes - BLUEPRINT - - EC:FP7:HEALTH2011-10-01 - 2016-09-30 - 282510 - VALID, Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), and Bierne, Hélène
Subjects: lcsh:QH426-470, Heterochromatin, Bisulfite sequencing, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Epigenetics, RNA-Directed DNA Methylation, Genetics (clinical), X chromosome, Original Research, 030304 developmental biology, Xi, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Autosome, DNA methylation, LAD, epigenetics, heterochromatin, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, cytosine methylation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], whole genome bisulfite sequencing, lcsh:Genetics, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Molecular Medicine, Illumina Methylation Assay, 030217 neurology & neurosurgery
Abstract: International audience; BAH domain-containing protein 1 (BAHD1) is involved in heterochromatin formation and gene repression in human cells. BAHD1 also localizes to the inactive X chromosome (Xi), but the functional significance of this targeting is unknown. So far, research on this protein has been hampered by its low endogenous abundance and its role in epigenetic regulation remains poorly explored. In this work, we used whole-genome bisulfite sequencing (BS-seq) to compare the DNA methylation profile of HEK293 cells expressing low levels of BAHD1 (HEK-CT) to that of isogenic cells stably overexpressing BAHD1 (HEK-BAHD1). We show that increasing BAHD1 levels induces de novo DNA methylation on autosomes and a marked hypomethylation on the X chromosome (chrX). We identified 91,358 regions that have different methylation patterns in HEK-BAHD1 compared to HEK-CT cells (termed "BAHD1-DMRs"), of which 83,850 mapped on autosomes and 7508 on the X chromosome (chrX). Autosomal BAHD1-DMRs were predominantly hypermethylated and located to satellites, interspersed repeats, and intergenic regions. In contrast, BAHD1-DMRs on chrX were mainly hypomethylated and located to gene bodies and enhancers. We further found that BAHD1-DMRs display a higher-order organization by being clustered within large chromosomal domains. Half of these "BAHD1-Associated differentially methylated Domains" (BADs) overlapped with lamina-associated domains (LADs). Based on these results, we propose that BAHD1-mediated heterochromatin formation is linked to DNA methylation and may play a role in the spatial architecture of the genome.
Published: 2015
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17. Organelle targeting during bacterial infection: insights from Listeria

Author: Alice Lebreton, Fabrizia Stavru, Pascale Cossart, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), financial support from Pasteur Institute, INSERM and INRA, from the European Research Council (ERC) advanced Grant 233348, from Agence Nationale de la Recherche (ANR blancs Mitopatho 12-BSV3-0017-03 and EpiLis 11-BSV3-003-01, ERA-NET Infect-ERA ProAntiLis), from Laboratoires d’Excellence (IBEID ANR-10- LABX-62-01), from Fondation Jeantet and Fondation le Roch Les Mousquetaires, ANR-12-BSV3-0017,MITOPATHO,Rôle des mitochondries durant l'invasion des cellules par les bactéries Listeria et Shigella(2012), ANR-11-BSV3-0003,EPILIS,Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes(2011), ANR-13-IFEC-0004,PROANTILIS,Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes(2013), ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut National de la Recherche Agronomique (INRA) - Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Epilepsies de l'Enfant et Plasticité Cérébrale, Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - AP-HP Hôpital Necker - Enfants Malades [Paris], ANR-12-BSV3-0017, MITOPATHO, Rôle des mitochondries durant l'invasion des cellules par les bactéries Listeria et Shigella(2012), ANR-11-BSV3-0003, EPILIS, Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes(2011), ANR-13-IFEC-0004, PROANTILIS, Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes(2013), ANR-10-LABX-62-IBEID, IBEID, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), European Project : 233348, MODELIST, École normale supérieure - Paris (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)-École normale supérieure - Paris (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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Cossart, Pascale, Lebreton, Alice, BLANC - Rôle des mitochondries durant l'invasion des cellules par les bactéries Listeria et Shigella - - MITOPATHO2012 - ANR-12-BSV3-0017 - BLANC - VALID, BLANC - Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes - - EPILIS2011 - ANR-11-BSV3-0003 - BLANC - VALID, ERA-NET Infect-ERA - Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes - - PROANTILIS2013 - ANR-13-IFEC-0004 - IFEC - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, and 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)
Subjects: organelle, Listeria, MESH: Bacterial Infections, MESH: Mitochondria, Cellular microbiology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Endoplasmic Reticulum, medicine.disease_cause, Listeria monocytogenes, cellular microbiology, mitochondria, nucleus, endomembrane system, MESH: Listeria monocytogenes, Microbiology, 03 medical and health sciences, Bacterial Proteins, MESH: Listeria, MESH: Endoplasmic Reticulum, Organelle, medicine, Animals, Humans, Endomembrane system, MESH: Animals, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Bacterial Proteins, 030304 developmental biology, 0303 health sciences, MESH: Humans, biology, 030306 microbiology, Intracellular parasite, Endoplasmic reticulum, Bacterial Infections, Cell Biology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Chromatin, Cell biology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Listeria monocytogenes, a facultative intracellular bacterium responsible for severe foodborne infections, is now recognized as a multifaceted model in infection biology. Comprehensive studies of the molecular and cellular basis of the infection have unraveled how the bacterium crosses the intestinal and feto-placental barriers, invades several cell types in which it multiplies and moves, and spreads from cell to cell. Interestingly, although Listeria does not actively invade host cell organelles, it can interfere with their function. We discuss the effect of Listeria on the endoplasmic reticulum (ER) and the mechanisms leading to the fragmentation of the mitochondrial network and its consequences, and review the strategies used by Listeria to subvert nuclear functions, more precisely to control host gene expression at the chromatin level.
Published: 2015

18. A trip in the 'New Microbiology' with the bacterial pathogen Listeria monocytogenes

Author: Alice Lebreton, Pascale Cossart, Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), financial support from Pasteur Institute, INSERM and INRA, from the European Research Council (ERC) advanced Grant 233348, from Agence Nationale de la Recherche (ANR BacNet 10-BINF-0201 and EpiLis 11-BSV3-003-01), from Laboratoires d’Excellence (IBEID ANR-10-LABX-62-01), from Fondation Jeantet and Fondation le Roch Les Mousquetaires., ANR: 10-BINF-02-01,BACNET,ANR, ANR-11-BSV3-0003,EPILIS,Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes(2011), ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), 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)-École normale supérieure - Paris (ENS-PSL), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-10-BINF-0002,BACNET,Exploring composition and dynamics of bacterial regulatory networks(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 233348,EC:FP7:ERC,ERC-2008-AdG,MODELIST(2009), Institut National de la Recherche Agronomique (INRA) - Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), ANR : 10-BINF-02-01, BACNET, ANR, ANR-11-BSV3-0003, EPILIS, Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes(2011), ANR-10-LABX-62-IBEID, IBEID, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), European Project : 233348, MODELIST, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (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)-École normale supérieure - Paris (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), Lebreton, Alice, Exploring composition and dynamics of bacterial regulatory networks - - BACNET2010 - ANR-10-BINF-0002 - BINF - VALID, BLANC - Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes - - EPILIS2011 - ANR-11-BSV3-0003 - BLANC - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Understanding the infection by the bacterium Listeria monocytogenes as a way to address key issues in biology - MODELIST - - EC:FP7:ERC2009-06-01 - 2015-05-31 - 233348 - VALID, and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris
Subjects: Transcription, Genetic, Cellular microbiology, medicine.disease_cause, MESH: Listeria monocytogenes, Biochemistry, Epigenesis, Genetic, Structural Biology, Listeriosis, MESH: Animals, MESH: Epigenesis, Genetic, Pathogen, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, biology, Non-coding RNA, Endocytosis, Chromatin, Host-Pathogen Interactions, Intracellular, Biophysics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Clathrin, Microbiology, 03 medical and health sciences, Listeria monocytogenes, Genetics, medicine, Animals, Humans, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, MESH: Humans, 030306 microbiology, MESH: Transcription, Genetic, MESH: Host-Pathogen Interactions, MESH: Chromatin Assembly and Disassembly, Cell Biology, Gene Expression Regulation, Bacterial, biology.organism_classification, Chromatin Assembly and Disassembly, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Listeriosis, biology.protein, Listeria, Mitochondrial dynamics, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Listeria monocytogenes is a food-borne pathogen causing an opportunistic disease called listeriosis. This bacterium invades and replicates in most cell types, due to its multiple strategies to exploit host molecular mechanisms. Research aiming at unravelling Listeria invasion and intracellular lifestyle has led to a number of key discoveries in infection biology, cell biology and also microbiology. In this review, we report on our most recent advances in understanding the intimate crosstalk between the bacterium and its host, resulting from in-depth studies performed over the past five years. We specifically highlight new concepts in RNA-based regulation in bacteria and discuss important findings in cell biology, including a new role for clathrin and an atypical mitochondrial fragmentation mechanism. We also illustrate the notion that bacterial infection regulates host gene expression at the chromatin level, contributing to an emerging field called patho-epigenetics. This review corresponds to the lecture given by one of us (P.C.) on the occasion of the 2014 FEBS|EMBO Woman in Science Award.
Published: 2014

19. The intestinal microbiota interferes with the microRNA response upon oral Listeria infection

Author: Pierre Lechat, Odile Sismeiro, Alice Lebreton, Constance Ciaudo, Joern Toedling, Christophe Bécavin, Guillaume Soubigou, Cristel Archambaud, Pascale Cossart, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris] (IP), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL), Génétique et Biologie du Développement, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génopole, European Research Council (E.R.C.) Advanced grant [233348], ANR Investissement d'Avenir Programme [10-LABX-62], Institut Pasteur, Institut National de la Sante et de la Recherche Medicale, Fondation Jeantet and Fondation le Roch, Federation of European Biochemical Societies, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 233348,EC:FP7:ERC,ERC-2008-AdG,MODELIST(2009), Lebreton, Alice, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Understanding the infection by the bacterium Listeria monocytogenes as a way to address key issues in biology - MODELIST - - EC:FP7:ERC2009-06-01 - 2015-05-31 - 233348 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Institut Pasteur [Paris], MINES ParisTech - École nationale supérieure des mines de Paris, Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], ANR-10-LABX-0062/10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Transcription, Genetic, Human pathogen, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, MOUSE, MESH: Listeria monocytogenes, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, IMMUNE-SYSTEM, MEDIATED REGULATION, MONOCYTOGENES, RECOGNITION, EXPRESSION, VIRULENCE, ESCAPE, CANCER, GUT, Transcriptome, Mice, 0302 clinical medicine, Listeriosis, MESH: Animals, Pathogen, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], biology, Microbiota, Life sciences, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], QR1-502, 3. Good health, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Research Article, Listeria infection, Microbiology, 03 medical and health sciences, MESH: Gene Expression Profiling, Immune system, Listeria monocytogenes, Ileum, MESH: Mice, Inbred C57BL, ddc:570, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, MESH: Microbiota, MESH: Mice, 030304 developmental biology, Gene Expression Profiling, MESH: Transcription, Genetic, MESH: Host-Pathogen Interactions, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Mice, Inbred C57BL, MicroRNAs, MESH: Listeriosis, MESH: Ileum, Immunology, Listeria, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Female, MESH: MicroRNAs
Abstract: The intestinal tract is the largest reservoir of microbes in the human body. The intestinal microbiota is thought to be able to modulate alterations of the gut induced by enteropathogens, thereby maintaining homeostasis. Listeria monocytogenes is the agent of listeriosis, an infection transmitted to humans upon ingestion of contaminated food. Crossing of the intestinal barrier is a critical step of the infection before dissemination into deeper organs. Here, we investigated the role of the intestinal microbiota in the regulation of host protein-coding genes and microRNA (miRNA or miR) expression during Listeria infection. We first established the intestinal miRNA signatures corresponding to the 10 most highly expressed miRNAs in the murine ileum of conventional and germfree mice, noninfected and infected with Listeria. Next, we identified 6 miRNAs whose expression decreased upon Listeria infection in conventional mice. Strikingly, five of these miRNA expression variations (in miR-143, miR-148a, miR-200b, miR-200c, and miR-378) were dependent on the presence of the microbiota. In addition, as is already known, protein-coding genes were highly affected by infection in both conventional and germfree mice. By crossing bioinformatically the predicted targets of the miRNAs to our whole-genome transcriptomic data, we revealed an miRNA-mRNA network that suggested miRNA-mediated global regulation during intestinal infection. Other recent studies have revealed an miRNA response to either bacterial pathogens or commensal bacteria. In contrast, our work provides an unprecedented insight into the impact of the intestinal microbiota on host transcriptional reprogramming during infection by a human pathogen., IMPORTANCE While the crucial role of miRNAs in regulating the host response to bacterial infection is increasingly recognized, the involvement of the intestinal microbiota in the regulation of miRNA expression has not been explored in detail. Here, we investigated the impact of the intestinal microbiota on the regulation of protein-coding genes and miRNA expression in a host infected by L. monocytogenes, a food-borne pathogen. We show that the microbiota interferes with the microRNA response upon oral Listeria infection and identify several protein-coding target genes whose expression correlates inversely with that of the miRNA. Further investigations of the regulatory networks involving miR-143, miR-148a, miR-200b, miR-200c, and miR-378 will provide new insights into the impact of the intestinal microbiota on the host upon bacterial infection.
Published: 2012

20. Bacteria tune interferon responses by playing with chromatin

Author: Hélène Bierne, Alice Lebreton, Pascale Cossart, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Nationale Contre le Cancer (LNCC RS10/75-76 Bierne), ANR-11-BSV3-0003,EPILIS,Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes(2011), European Project: 233348,MODELIST, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lebreton, Alice, BLANC - Reprogrammation épigénétique par la bactérie pathogène Listeria monocytogenes - - EPILIS2011 - ANR-11-BSV3-0003 - BLANC - VALID, ERC Advanced grant - MODELIST - 233348 - INCOMING, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA)
Subjects: Chromosomal Proteins, Non-Histone, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, MESH: Listeria monocytogenes, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Mice, Interferon, MESH: Animals, MESH: Interferons, Listeriosis, Pathogen, Chromatin, 3. Good health, Infectious Diseases, Host-Pathogen Interactions, medicine.drug, Microbiology (medical), BAHD1, Listeria, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Microbiology, Mycobacterium, MESH: Chromatin, Listeria monocytogenes, MESH: Chromosomal Proteins, Non-Histone, medicine, Animals, Humans, Secretion, Epigenetics, chromatin complex, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Gene, MESH: Mice, Innate immune system, MESH: Humans, epigenetics, MESH: Host-Pathogen Interactions, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Listeriosis, interferon-lambda, Parasitology, Interferons, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Bacterial infections, like their viral counterparts, trigger the onset of innate immune defense mechanisms through the release of cytokines, including interferons (IFNs). While type I and II IFN responses to bacteria have long been explored, type III IFN response remains poorly addressed. We have recently reported that the pathogen Listeria monocytogenes triggers the expression of type I and III IFN genes in epithelial cells, and is able to fine-tune downstream signaling at the chromatin level. This bacterium can negatively or positively modulate the expression of interferon-stimulated genes (ISGs) by manipulating the function of BAHD1, a component of a host chromatin-silencing complex. To this end, L. monocytogenes tightly controls the secretion of a BAHD1 inhibitory factor, LntA. Here, we further document the current knowledge about chromatin mechanisms modulating interferon responses during host-bacteria interplay, and discuss their physiological consequences.
Published: 2012

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20 results on '"Lebreton, Alice"'

1. Fluorescent secreted bacterial effectors reveal active intravacuolar proliferation of Listeria monocytogenes in epithelial cells

2. An alternative replication niche for Listeria monocytogenes revealed by fluorescent tagging of bacterial secreted effectors

3. Listeriolysin O promotes the intravacuolar growth of Listeria monocytogenes in epithelial cells

4. Régulations post-transcriptionnelles de l'expression génique de la cellule hôte en réponse à l'infection bactérienne

5. Dynamics of pre-ribosomal factors along the large ribosomal subunit biogenesis in S. cerevisiae

6. Dynamics of pre-ribosomal factors along the large ribosomal subunit biogenesis in S. cerevisiae

7. Adaptations of intracellular bacteria to vacuolar or cytosolic niches

8. Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism

9. Visualizing the dynamics of exported bacterial proteins with the chemogenetic fluorescent reporter FAST

10. Coordination of transcriptional and translational regulations in human cells infected by Listeria monocytogenes

11. ALFA: annotation landscape for aligned reads

12. Coordination of transcriptional and translational regulations in human cells infected by Listeria monocytogenes

13. Listeriolysin O promotes the intravacuolar growth of Listeria monocytogenes in epithelial cells

14. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression

15. 1926–2016: 90 Years of listeriology

16. Overexpression of the Heterochromatinization Factor BAHD1 in HEK293 Cells Differentially Reshapes the DNA Methylome on Autosomes and X Chromosome

17. Organelle targeting during bacterial infection: insights from Listeria

18. A trip in the 'New Microbiology' with the bacterial pathogen Listeria monocytogenes

19. The intestinal microbiota interferes with the microRNA response upon oral Listeria infection

20. Bacteria tune interferon responses by playing with chromatin

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