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23 results on '"Mathieu Coureuil"'

1. Multitasking Actors of Staphylococcus aureus Metabolism and Virulence

Author

Xin Tan, Mathieu Coureuil, Anne Jamet, Alain Charbit, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Charbit, Alain, and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microbiology (medical), Staphylococcus aureus, Virulence, Biology, medicine.disease_cause, Microbiology, Pathogenesis, 03 medical and health sciences, Virology, medicine, Animals, Humans, Human multitasking, Amino acid metabolism, Amino Acids, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Fatty Acids, Metabolism, Staphylococcal Infections, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biosynthetic Pathways, 3. Good health, virulence, Metabolic pathway, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Biochemistry, Nucleic acid, Carbohydrate Metabolism, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, metabolism, Metabolic Networks and Pathways
Abstract

International audience; Recent studies have uncovered the striking commonality of multitasking molecular actors linking metabolism and virulence regulation. Beyond the well known importance of carbohydrate and amino acid metabolism regulators in coordinating metabolic pathways and pathogenesis, we highlight recent major advances linking lipid and nucleic acid pathways to virulence regulation in Staphylococcus aureus.

Published
2020

2. Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence

Author

Agnès Ferroni, Alain Charbit, Fabiola Tros, Xavier Nassif, Ida Chiara Guerrera, Daniel Euphrasie, Mathieu Coureuil, Ivan Nemanzny, Cerina Chhuon, Elodie Ramond, Isabelle Sermet-Gaudelus, Julie Meyer, Anne Jamet, Marion Dupuis, Xin Tan, Charbit, Alain, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Canalopathies épithéliales: la mucoviscidose et autres maladies, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
Proteomics, 0301 basic medicine, Microbiology (medical), Staphylococcus aureus, medicine.drug_class, 030106 microbiology, Antibiotics, Virulence, Biology, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, biofilm, Cell Line, Persistence (computer science), Microbiology, cystic fibrosis, 03 medical and health sciences, Tandem Mass Spectrometry, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Pathogen, Cells, Cultured, Proteogenomics, 030304 developmental biology, 0303 health sciences, Lung, 030306 microbiology, business.industry, Biofilm, intracellular persistence, medicine.disease, Adaptation, Physiological, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Anti-Bacterial Agents, 3. Good health, proteogenomics, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Biofilms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Intracellular, Chromatography, Liquid
Abstract

BackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.MethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.ResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.Furthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.ConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.SummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.

Published
2019

3. The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus

Author

Philippe Morand, Lisa Craig, Subramania Kolappan, Marion Dupuis, Jean-Philippe Barnier, Haniaa Bouzinba-Segard, Julie Meyer, Emmanuelle Bille, Taliah Schmitt, Eric Frapy, Elena Capel, Gaël Gesbert, Sophia Schönherr-Hellec, Anne Jamet, Sandrine Bourdoulous, Xavier Nassif, Zoé Virion, Mathieu Coureuil, Coureuil, Mathieu, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Simon Fraser University (SFU.ca), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre hospitalier Saint-Joseph [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Pilus assembly, Mutant, Drug Evaluation, Preclinical, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Mice, SCID, Neisseria meningitidis, medicine.disease_cause, Pilus, Antibodies, Bacterial Adhesion, Microbiology, Cell Line, 03 medical and health sciences, Bacterial Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Antigenic variation, Animals, Humans, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, Chemistry, Alanine scanning, biochemical phenomena, metabolism, and nutrition, Biological Sciences, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Bacterial adhesin, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Meningococcal Infections, Pilin, Fimbriae, Bacterial, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, bacteria, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Neisseria meningitidis utilizes type IV pili (T4P) to adhere to and colonize host endothelial cells, a process at the heart of meningococcal invasive diseases leading to meningitis and sepsis. T4P are polymers of an antigenically variable major pilin building block, PilE, plus several core minor pilins that initiate pilus assembly and are thought to be located at the pilus tip. Adhesion of N. meningitidis to human endothelial cells requires both PilE and a conserved noncore minor pilin PilV, but the localization of PilV and its precise role in this process remains to be clarified. Here, we show that both PilE and PilV promote adhesion to endothelial vessels in vivo. The substantial adhesion defect observed for pilV mutants suggests it is the main adhesin. Consistent with this observation, superresolution microscopy showed the abundant distribution of PilV throughout the pilus. We determined the crystal structure of PilV and modeled it within the pilus filament. The small size of PilV causes it to be recessed relative to adjacent PilE subunits, which are dominated by a prominent hypervariable loop. Nonetheless, we identified a conserved surface-exposed adhesive loop on PilV by alanine scanning mutagenesis. Critically, antibodies directed against PilV inhibit N. meningitidis colonization of human skin grafts. These findings explain how N. meningitidis T4P undergo antigenic variation to evade the humoral immune response while maintaining their adhesive function and establish the potential of this highly conserved minor pilin as a vaccine and therapeutic target for the prevention and treatment of N. meningitidis infections.

Published
2021

4. High-Resolution Typing of Staphylococcus epidermidis Based on Core Genome Multilocus Sequence Typing To Investigate the Hospital Spread of Multidrug-Resistant Clones

Author

Sylvain Brisse, Johanna Roux, Jean-Philippe Barnier, Emmanuelle Bille, Mathieu Coureuil, Daniel Euphrasie, Alain Charbit, Christine Bole-Feysot, Anne Jamet, Julie Meyer, Xavier Nassif, Jean-François Magny, Julien Guglielmini, Bryan Brancotte, Agnès Ferroni, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biodiversité et Biotechnologie Fongiques (BBF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Contrat de Recherche Clinique, French Ministry of Health CRC17040, Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-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 Cité (UPCité), Institut Pasteur [Paris] (IP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Charbit, Alain

Subjects
Microbiology (medical), Epidemiology, Locus (genetics), Genome, 03 medical and health sciences, Staphylococcus epidermidis, Humans, Typing, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Gene, Pathogen, 030304 developmental biology, Genetics, 0303 health sciences, biology, 030306 microbiology, Staphylococcal Infections, biology.organism_classification, Hospitals, Clone Cells, 3. Good health, Multiple drug resistance, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Multilocus sequence typing, Genome, Bacterial, Multilocus Sequence Typing
Abstract

International audience; ABSTRACT Staphylococcus epidermidis is a pathogen emerging worldwide as a leading cause of health care-associated infections. A standardized high-resolution typing method to document transmission and dissemination of multidrug-resistant S. epidermidis strains is needed. Our aim was to provide a core genome multilocus sequence typing (cgMLST) scheme for S. epidermidis to improve the international surveillance of S. epidermidis . We defined a cgMLST scheme based on 699 core genes and used it to investigate the population structure of the species and the genetic relatedness of isolates recovered from infants hospitalized in several wards of a French hospital. Our results show the long-lasting endemic persistence of S. epidermidis clones within and across wards of hospitals and demonstrate the ability of our cgMLST approach to identify and track these clones. We made the scheme publicly available through the Institut Pasteur BIGSdb server ( http://bigsdb.pasteur.fr/epidermidis/ ). This tool should enable international harmonization of the epidemiological surveillance of multidrug-resistant S. epidermidis clones. By comparing gene distribution among infection and commensal isolates, we also confirmed the association of the mecA locus with infection isolates and of the fdh gene with commensal isolates. (This study has been registered at ClinicalTrials.gov under registration no. NCT03374371.)

Published
2021

5. Type IV pilus retraction enables sustained bacteremia and plays a key role in the outcome of meningococcal sepsis in a humanized mouse model

Author

Mathieu Coureuil, Taliah Schmitt, Xavier Nassif, Sandrine Bourdoulous, Mohamed El Behi, Daniel Euphrasie, Olivier Join-Lambert, Mathilde Audry, Sophia Schönherr-Hellec, Jean-Philippe Barnier, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), [Institut Cochin] Departement Infection, immunité, inflammation, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Bourdoulous, Sandrine

Subjects
Bacterial Diseases, Bacterial Lethality, Physiology, Bacteremia, Mice, SCID, Meningococcal Disease, Pilus retraction, Neisseria meningitidis, Pathology and Laboratory Medicine, medicine.disease_cause, Bacterial Adhesion, Pilus, Mice, Medical Conditions, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Biology (General), Immune Response, 0303 health sciences, Skin Transplantation, Bacterial Pathogens, Body Fluids, 3. Good health, Infectious Diseases, Blood, Medical Microbiology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Fimbriae Proteins, Pathogens, Cellular Structures and Organelles, Anatomy, medicine.symptom, Neisseria, Research Article, Pathogen Motility, QH301-705.5, Virulence Factors, Immunology, Inflammation, Biology, Meningococcal disease, Microbiology, Sepsis, 03 medical and health sciences, Signs and Symptoms, Virology, Genetics, medicine, Animals, Humans, Microbial Pathogens, Molecular Biology, 030304 developmental biology, Bacteria, 030306 microbiology, Organisms, Endothelial Cells, Biology and Life Sciences, Bacteriology, Cell Biology, RC581-607, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Meningococcal Infections, Disease Models, Animal, Pili and Fimbriae, Fimbriae, Bacterial, Humanized mouse, Parasitology, Immunologic diseases. Allergy, Clinical Medicine, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

Neisseria meningitidis (the meningococcus) remains a major cause of bacterial meningitis and fatal sepsis. This commensal bacterium of the human nasopharynx can cause invasive diseases when it leaves its niche and reaches the bloodstream. Blood-borne meningococci have the ability to adhere to human endothelial cells and rapidly colonize microvessels. This crucial step enables dissemination into tissues and promotes deregulated inflammation and coagulation, leading to extensive necrotic purpura in the most severe cases. Adhesion to blood vessels relies on type IV pili (TFP). These long filamentous structures are highly dynamic as they can rapidly elongate and retract by the antagonistic action of two ATPases, PilF and PilT. However, the consequences of TFP dynamics on the pathophysiology and the outcome of meningococcal sepsis in vivo have been poorly studied. Here, we show that human graft microvessels are replicative niches for meningococci, that seed the bloodstream and promote sustained bacteremia and lethality in a humanized mouse model. Intriguingly, although pilus-retraction deficient N. meningitidis strain (ΔpilT) efficiently colonizes human graft tissue, this mutant did not promote sustained bacteremia nor induce mouse lethality. This effect was not due to a decreased inflammatory response, nor defects in bacterial clearance by the innate immune system. Rather, TFP-retraction was necessary to promote the release of TFP-dependent contacts between bacteria and, in turn, the detachment from colonized microvessels. The resulting sustained bacteremia was directly correlated with lethality. Altogether, these results demonstrate that pilus retraction plays a key role in the occurrence and outcome of meningococcal sepsis by supporting sustained bacteremia. These findings open new perspectives on the role of circulating bacteria in the pathological alterations leading to lethal sepsis., Author summary Invasive meningococcal diseases remain a major cause of fatal sepsis. A specific feature of Neisseria meningitidis is its ability to colonize the blood microvessels in a type IV pilus (TFP)-dependent mechanism. TFP are filamentous appendages that undergo retraction through a mechanism dependent on the PilT ATPase. Here, we assess the role of TFP retraction in the pathophysiology of meningococcal infection using a humanized model of SCID mice grafted with human skin. We show that human skin graft microvessels are replicative niches for N. meningitidis that promote sustained bacteremia and subsequent lethality. Intriguingly, although pilus retraction-deficient N. meningitidis (ΔpilT) efficiently colonizes human grafts, this mutant strain did not promote sustained bacteremia nor induce mouse lethality. This drastic decrease in virulence was not due to a decreased inflammatory response or to a defect in bacterial clearance by the innate immune system. Rather, we demonstrate that pilus retraction was crucial to obtain a sustained bacteremia by allowing the release of bacteria from colonized microvessels and that lethality was directly linked to sustained bacteremia. Altogether, these data demonstrate the important role of pilus retraction in meningococcal pathogenesis and infection outcome and open new questions regarding the impact of circulating bacteria on the host during lethal sepsis.

Published
2021

6. Reactive Oxygen Species-Dependent Innate Immune Mechanisms Control Methicillin-Resistant Staphylococcus aureus Virulence in the Drosophila Larval Model

Author

Mathieu Coureuil, Laurence Arbibe, Daniel Euphrasie, Louison Lallemant, Clémence Bouvier, Xiongqi Ding, Elodie Ramond, Alain Charbit, Anne Jamet, Xiangyan He, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Charbit, Alain

Subjects
Methicillin-Resistant Staphylococcus aureus, Pore Forming Cytotoxic Proteins, Staphylococcus aureus, Virulence, medicine.disease_cause, Microbiology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, intestinal infection, 03 medical and health sciences, Duox, Shigella flexneri, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Animals, Antimicrobial peptide production, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, 0303 health sciences, Innate immune system, biology, 030306 microbiology, catalase, Gene Expression Regulation, Bacterial, Staphylococcal Infections, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, biology.organism_classification, Methicillin-resistant Staphylococcus aureus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, QR1-502, 3. Good health, virulence, Disease Models, Animal, Drosophila melanogaster, Salmonella enterica, Larva, Host-Pathogen Interactions, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Reactive Oxygen Species, Research Article, gastrointestinal infection
Abstract

Antibiotic-resistant Staphylococcus aureus strains constitute a major public health concern worldwide and are responsible for both health care- and community-associated infections. Here, we establish a robust and easy-to-implement model of oral S. aureus infection using Drosophila melanogaster larvae that allowed us to follow the fate of S. aureus at the whole-organism level as well as the host immune responses. Our study demonstrates that S. aureus infection triggers H2O2 production by the host via the Duox enzyme, thereby promoting antimicrobial peptide production through activation of the Toll pathway. Staphylococcal catalase mediates H2O2 neutralization, which not only promotes S. aureus survival but also minimizes the host antimicrobial response, hence reducing bacterial clearance in vivo. We show that while catalase expression is regulated in vitro by the accessory gene regulatory system (Agr) and the general stress response regulator sigma B (SigB), it no longer depends on these two master regulators in vivo. Finally, we confirm the versatility of this model by demonstrating the colonization and host stimulation capabilities of S. aureus strains belonging to different sequence types (CC8 and CC5) as well as of two other bacterial pathogens, Salmonella enterica serovar Typhimurium and Shigella flexneri. Thus, the Drosophila larva can be a general model to follow in vivo the innate host immune responses triggered during infection by human pathogens. IMPORTANCE The pathogenicity of methicillin-resistant S. aureus (MRSA) strains relies on their ability to produce a wide variety of tightly regulated virulence factors. Current in vivo models to analyze host-pathogen interactions are limited and difficult to manipulate. Here, we have established a robust and reliable model of oral S. aureus infection using Drosophila melanogaster larvae. We show that S. aureus stimulates host immunity through the production of reactive oxygen species (ROS) and antimicrobial peptide (AMP) and that ROS potentialize AMP gene expression. S. aureus catalase plays a key role in this complex environment and acts in vivo independently from SigB and Agr control. We propose that fly larvae can provide a general model for studying the colonization capabilities of human pathogens.

Published
2021

7. Which Current and Novel Diagnostic Avenues for Bacterial Respiratory Diseases?

Author

Héloïse Rytter, Anne Jamet, Mathieu Coureuil, Alain Charbit, Elodie Ramond, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Paris Descartes - Paris 5 (UPD5)-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 Cité (UPCité), and Charbit, Alain

Subjects
Microbiology (medical), medicine.medical_specialty, respiratory tract infection, lcsh:QR1-502, Review, medicine.disease_cause, Microbiology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:Microbiology, 03 medical and health sciences, 0302 clinical medicine, rapid test, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, 030212 general & internal medicine, Intensive care medicine, 030304 developmental biology, [SDV.IB] Life Sciences [q-bio]/Bioengineering, 0303 health sciences, Lung, business.industry, Diagnostic test, Pathogenic bacteria, medicine.disease, artificial intelligence, 3. Good health, Pneumonia, lung disease (diagnosis), medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, diagnostic test, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Acute pneumonia, business
Abstract

International audience; Bacterial acute pneumonia is responsible for an extremely large burden of death worldwide and diagnosis is paramount in the management of patients. While multidrug-resistant bacteria is one of the biggest health threats in the coming decades, clinicians urgently need access to novel diagnostic technologies. In this review, we will first present the already existing and largely used techniques that allow identifying pathogen-associated pneumonia. Then, we will discuss the latest and most promising technological advances that are based on connected technologies (artificial intelligence-based and Omics-based) or rapid tests, to improve the management of lung infections caused by pathogenic bacteria. We also aim to highlight the mutual benefits of fundamental and clinical studies for a better understanding of lung infections and their more efficient diagnostic management.

Published
2020

8. Receptor recognition by meningococcal type IV pili relies on a specific complex N-glycan

Author

Haniaa Bouzinba-Segard, Mathieu Coureuil, Catherine Robbe-Masselot, Xavier Nassif, Zoé Virion, Sandrine Bourdoulous, Renaud Léonard, Loic Le Guennec, Université de Lille, LillOA, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (UMR_S567 / UMR 8104), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lille, CNRS, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Université Paris Descartes - Paris 5 [UPD5], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], and Institut Cochin [UMR_S567 / UMR 8104]

Subjects
Glycan, [SDV]Life Sciences [q-bio], Biology, Neisseria meningitidis, medicine.disease_cause, Pilus, Microbiology, type IV pili, host–pathogen interaction, virulence, glycan, 03 medical and health sciences, 0302 clinical medicine, medicine, Receptor, Tropism, Fucosylation, 030304 developmental biology, 0303 health sciences, Multidisciplinary, 3. Good health, Bacterial adhesin, [SDV] Life Sciences [q-bio], Basigin, biology.protein, 030217 neurology & neurosurgery
Abstract

Bacterial infections are frequently based on the binding of lectin-like adhesins to specific glycan determinants exposed on host cell receptors. These interactions confer species-specific recognition and tropism for particular host tissues and represent attractive antibacterial targets. However, the wide structural diversity of carbohydrates hampers the characterization of specific glycan determinants. Here, we characterized the receptor recognition of type IV pili (Tfp), a key adhesive factor present in numerous bacterial pathogens, using Neisseria meningitidis as a model organism. We found that meningococcal Tfp specifically recognize a triantennary sialylated poly- N -acetyllactosamine–containing N -glycan exposed on the human receptor CD147/Basigin, while fucosylated derivatives of this N -glycan impaired bacterial adhesion. Corroborating the inhibitory role of fucosylation on receptor recognition, adhesion of the meningococcus on nonhuman cells expressing human CD147 required prior defucosylation. These findings reveal the molecular basis of the selective receptor recognition by meningococcal Tfp and thereby, identify a potential antibacterial target.

Published
2020

9. Critical Role of a Sheath Phosphorylation Site On the Assembly and Function of an Atypical Type VI Secretion System

Author

Mathieu Coureuil, Ida Chiara Guerrera, Guénolé Prigent, Claire Lays, Monique Barel, Fabiola Tros, Nicholas H. Keep, Jason Ziveri, Alain Charbit, Anne Jamet, Cerina Chhuon, Héloïse Rytter, Thomas Henry, Pathogénie des infections systémiques (Inserm U1002), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Pathogénie des infections systémiques (UMR_S 570), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of London [London], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), U1002, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-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)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Charbit, Alain

Subjects
Proteomics, Stimulation, Biochemistry, Gas Chromatography-Mass Spectrometry, Analytical Chemistry, Cell Line, Potassium Chloride, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Tandem Mass Spectrometry, Humans, Secretion, Phosphorylation, Francisella tularensis, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Type VI secretion system, Alanine, 0303 health sciences, Electronic Data Processing, Phosphomimetics, biology, Molecular Structure, Research, Macrophages, 030302 biochemistry & molecular biology, Type VI Secretion Systems, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Mutagenesis, Site-Directed, Francisella, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Protein Processing, Post-Translational, Biogenesis
Abstract

The bacterial pathogen Francisella tularensis possesses a noncanonical type VI secretion system (T6SS) that is required for phagosomal escape in infected macrophages. KCl stimulation has been previously used to trigger assembly and secretion of the T6SS in culture. By differential proteomics, we found here that the amounts of the T6SS proteins remained unchanged upon KCl stimulation, suggesting involvement of post-translational modifications in T6SS assembly. A phosphoproteomic analysis indeed identified a unique phosphorylation site on IglB, a key component of the T6SS sheath. Substitutions of Y139 with alanine or phosphomimetics prevented T6SS formation and abolished phagosomal escape whereas substitution with phenylalanine delayed but did not abolish phagosomal escape in J774-1 macrophages. Altogether our data demonstrated that the Y139 site of IglB plays a critical role in T6SS biogenesis, suggesting that sheath phosphorylation could participate to T6SS dynamics. Data are available via ProteomeXchange with identifier PXD013619; and on MS-Viewer, key lkaqkllxwx.

Published
2019

10. Meningococcal disease: A paradigm of type-IV pilus dependent pathogenesis

Author

Philippe Morand, Mathieu Coureuil, Xavier Nassif, Isabel dos Santos Souza, Nawal Maïssa, Sandrine Bourdoulous, and Jason Ziveri

Subjects
Immunology, Target type, Virulence, Biology, Neisseria meningitidis, Meningococcal disease, medicine.disease_cause, Microbiology, Pilus, Bacterial Adhesion, Pathogenesis, 03 medical and health sciences, Mice, Virology, medicine, Animals, Humans, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Endothelial Cells, medicine.disease, Meningococcal Infections, Fimbriae, Bacterial, Meningitis, Purpura fulminans
Abstract

Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and meningitis. Interaction with both peripheral and cerebral microvascular endothelial cells is at the heart of meningococcal pathogenesis. During the last two decades, an essential role for meningococcal type IV pili in vascular colonisation and disease progression has been unravelled. This review summarises 20 years of research on meningococcal type IV pilus-dependent virulence mechanisms, up to the identification of promising anti-virulence compounds that target type IV pili.

Published
2019

11. Strategies used by bacterial pathogens to cross the blood–brain barrier

Author

Xavier Nassif, Sandrine Bourdoulous, Mathieu Coureuil, Loic Le Guennec, Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), SIGMA Clermont (SIGMA Clermont)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), U1002, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure des Mines de St Etienne

Subjects
Virulence Factors, [SDV]Life Sciences [q-bio], Immunology, Biology, Neisseria meningitidis, medicine.disease_cause, Blood–brain barrier, Microbiology, 03 medical and health sciences, Virology, Streptococcus pneumoniae, medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Inflammation, 0303 health sciences, Bacteria, 030306 microbiology, Streptococcus, Meninges, Brain, Endothelial Cells, Pathogenic bacteria, Biological Transport, medicine.disease, biology.organism_classification, 3. Good health, medicine.anatomical_structure, Blood-Brain Barrier, Meningitis
Abstract

The skull, spine, meninges, and cellular barriers at the blood-brain and the blood-cerebrospinal fluid interfaces well protect the brain and meningeal spaces against microbial invasion. However, once in the bloodstream, a range of pathogenic bacteria is able to reach the brain and cause meningitis. Despite advances in antibacterial therapy, bacterial meningitis remains one of the most important infectious diseases worldwide. The most common causative bacteria in children and adults are Streptococcus pneumoniae and Neisseria meningitidis associated with high morbidity and mortality, while among neonates, most cases of bacterial meningitis are due to group B Streptococcus and Escherichia coli. Here we summarise our current knowledge on the strategies used by these bacterial pathogens to survive in the bloodstream, to colonise the brain vasculature and to cross the blood-brain barrier.

Published
2019

12. Molecular interactions between Neisseria meningitidis and its human host

Author

Xavier Nassif, Sandrine Bourdoulous, Hervé Lécuyer, Anne Jamet, Mathieu Coureuil, Emmanuelle Bille, U1002, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Panthéon-Assas (UP2), Institut Cochin (IC UM3 (UMR 8104 / U1016)), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Virulence Factors, [SDV]Life Sciences [q-bio], Immunology, Bacterial Toxins, Virulence, Inflammation, Neisseria meningitidis, medicine.disease_cause, Microbiology, 03 medical and health sciences, Inovirus, Virology, Nasopharynx, medicine, Extracellular, Humans, Pathogen, Special Issue ‐ Review, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Disseminated intravascular coagulation, 0303 health sciences, Special Issue ‐ Reviews, biology, Host Microbial Interactions, 030306 microbiology, Endothelial Cells, Epithelial Cells, biology.organism_classification, medicine.disease, 3. Good health, Colonisation, Meningococcal Infections, Blood Vessels, medicine.symptom, Bacteria
Abstract

Neisseria meningitidis is a Gram‐negative bacterium that asymptomatically colonises the nasopharynx of humans. For an unknown reason, N. meningitidis can cross the nasopharyngeal barrier and invade the bloodstream where it becomes one of the most harmful extracellular bacterial pathogen. This infectious cycle involves the colonisation of two different environments. (a) In the nasopharynx, N. meningitidis grow on the top of mucus‐producing epithelial cells surrounded by a complex microbiota. To survive and grow in this challenging environment, the meningococcus expresses specific virulence factors such as polymorphic toxins and MDAΦ. (b) Meningococci have the ability to survive in the extra cellular fluids including blood and cerebrospinal fluid. The interaction of N. meningitidis with human endothelial cells leads to the formation of typical microcolonies that extend overtime and promote vascular injury, disseminated intravascular coagulation, and acute inflammation. In this review, we will focus on the interplay between N. meningitidis and these two different niches at the cellular and molecular level and discuss the use of inhibitors of piliation as a potent therapeutic approach.

Published
2019

13. Air-interfaced colonization model suggests a commensal-like interaction of Neisseria meningitidis with the epithelium, which benefit from colonization by Streptococcus mitis

Author

Benoit Gachet, Renaud Léonard, Mathilde Audry, Barnier J, Bruno Saubaméa, Alain Schmitt, Xavier Nassif, Sophia Schönherr-Hellec, Mathieu Coureuil, and Catherine Robbe-Masselot

Subjects
0303 health sciences, Innate immune system, biology, 030306 microbiology, Neisseria meningitidis, medicine.disease_cause, biology.organism_classification, Commensalism, Mucus, Microbiology, Moraxella catarrhalis, 03 medical and health sciences, Streptococcus mitis, medicine, Colonization, Pathogen, 030304 developmental biology
Abstract

Neisseria meningitidisis an inhabitant of the nasopharynx, from which it is transmitted from person to person or disseminates in the blood and becomes a harmful pathogen. In this work, we addressed the colonization of the nasopharyngeal niche by focusing on the interplay between meningococci and the mucus that lines the mucosa of the host. Using Calu-3 cells grown in air-interfaced culture, we studied the meningococcal colonization of the mucus and the host response. Our results suggested thatN. meningitidisbehaved like commensal bacteria in mucus, without interacting with human cells or actively transmigrating through the cell layer. As such, meningococci did not trigger a strong innate immune response from the Calu-3 cells. Finally, we have shown that this model is suitable for studying interaction ofN. meningitidiswith other bacteria living in the nasopharynx, and thatStreptococcus mitisbut notMoraxella catarrhaliscan promote meningococcal growth in this model.

Published
2019
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14. Targeting Type IV pili as an antivirulence strategy against invasive meningococcal disease

Author

Jean-Philippe Barnier, Haniaa Bouzinba-Segard, Anne Gouge, Anne Jamet, Mathieu Coureuil, Philippe Morand, Xavier Nassif, Philippe Pelissier, Frank Lafont, Béatrice Durel, Marion Le Bris, Sandrine Bourdoulous, Olivier Join-Lambert, Nicolas Barois, Daniel Euphrasie, Kevin Denis, Loic Le Guennec, Camille Faure, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre hospitalier Saint-Joseph [Paris], K.D. and L.LG. were supported by a doctoral fellowship from la Region Ile de France and the Fondation pour la Recherche Médicale, respectively. This work was supported by collaborative research grants from the Agence Nationale de la Recherche of France (grant no. ANR-14-IFEC14-0006) to S.B. and X.N. in the framework of the Infect-ERA joint transnational call (European funding for infectious diseases research), by the Société d’Accélération du Transfert de Technologie (grant no. ANR-10-SATT-05-01) to S.B. and by grant no. ANR-10-EQPX-04-01 to F.L., We thank M. Robert-Genthon and F. Chretien for providing the P. aeruginosa PAO1 strain and brain tissues, M. Favier of the histology facility, A. Schmitt and T. Guilbert of the imaging facility, and K. Bailly and M. Andrieu of the cytometry facility of the Institut Cochin for their expert technical help., ANR-10-SATT-0005,SATT Erganeo,ERGANEO(2010), ANR-10-EQPX-0004,Imaginex BioMed,Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution(2010), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), ANR-10-SATT-0005,SATT ERGANEO,SATT ERGANEO (EX IDF INNOV)(2010), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Groupe hospitalier Paris Saint-Joseph - Hôpital, ANR: 10-SATT-0005,SATT IDF INNOV,IDF INNOV(2010), and ANR-10-EQPX-0004/10-EQPX-0004,Imaginex BioMed,Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution(2010)

Subjects
Microbiology (medical), Gram-negative bacteria, Immunology, Fimbria, Inflammation, medicine.disease_cause, Applied Microbiology and Biotechnology, Microbiology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virulence factor, Pilus, Bacterial genetics, 03 medical and health sciences, Genetics, medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Neisseria meningitidis, Cell Biology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine.symptom, Bacteria
Abstract

Bacterial virulence factors are attractive targets for the development of therapeutics. Type IV pili, which are associated with a remarkable array of properties including motility, the interaction between bacteria and attachment to biotic and abiotic surfaces, represent particularly appealing virulence factor targets. Type IV pili are present in numerous bacterial species and are critical for their pathogenesis. In this study, we report that trifluoperazine and related phenothiazines block functions associated with Type IV pili in different bacterial pathogens, by affecting piliation within minutes. Using Neisseria meningitidis as a paradigm of Gram-negative bacterial pathogens that require Type IV pili for pathogenesis, we show that piliation is sensitive to altered activity of the Na+ pumping NADH–ubiquinone oxidoreductase (Na+−NQR) complex and that these compounds probably altered the establishment of the sodium gradient. In vivo, these compounds exert a strong protective effect. They reduce meningococcal colonization of the human vessels and prevent subsequent vascular dysfunctions, intravascular coagulation and overwhelming inflammation, the hallmarks of invasive meningococcal infections. Finally, they reduce lethality. This work provides a proof of concept that compounds with activity against bacterial Type IV pili could beneficially participate in the treatment of infections caused by Type IV pilus-expressing bacteria. Phenothiazines inhibit Type IV pili function in Neisseria meningitidis and protect against bacterial colonization of blood vessels and lethality during infection.

Published
2019

15. Methods to Study the Roles of β-Arrestins in Meningococcal Signaling

Author

Stefano Marullo, Mathieu Coureuil, and Zoé Virion

Subjects
0303 health sciences, 030306 microbiology, Chemistry, Neisseria meningitidis, macromolecular substances, Adhesion, medicine.disease_cause, Pilus, Cell biology, 03 medical and health sciences, Ezrin, medicine, Signal transduction, Receptor, Actin, Diplococcus, 030304 developmental biology
Abstract

Neisseria meningitidis is a Gram-negative diplococcus restricted to humans that causes severe septicemia and/or meningitidis. Initial adhesion to human endothelial cells is mediated through the interaction of type IV pili with the hetero-oligomeric complexes formed by the human receptors CD147 and the β2-adrenergic receptor. Interaction with this complex heterodimer activates a β-arrestin-biased signaling pathway leading to actin polymerization and accumulation of ezrin and ezrin-binding partners. These signaling events promote the formation of cell plasma membrane protrusions in endothelial cells, which are crucial for N. meningitidis colonies to resist shear stress and colonize blood vessels. Here we provide detailed protocols to evaluate the role of β-arrestins in actin and ezrin signaling downstream of G protein-coupled receptor activation.

Published
2019

16. Neisseria meningitidiscolonization of the brain endothelium and cerebrospinal fluid invasion

Author

Mathieu Coureuil, Florence Miller, Olivier Join-Lambert, Xavier Nassif, Stefano Marullo, Hervé Lécuyer, and Sandrine Bourdoulous

Subjects
0303 health sciences, Endothelium, 030306 microbiology, Neisseria meningitidis, Immunology, Fimbria, Central nervous system, Biology, medicine.disease_cause, Blood–brain barrier, Microbiology, Pilus, 3. Good health, 03 medical and health sciences, Cerebrospinal fluid, medicine.anatomical_structure, Virology, medicine, Intracellular, 030304 developmental biology
Abstract

The brain and meningeal spaces are protected from bacterial invasion by the blood-brain barrier, formed by specialized endothelial cells and tight intercellular junctional complexes. However, once in the bloodstream, Neisseria meningitidis crosses this barrier in about 60% of the cases. This highlights the particular efficacy with which N. meningitidis targets the brain vascular cell wall. The first step of central nervous system invasion is the direct interaction between bacteria and endothelial cells. This step is mediated by the type IV pili, which induce a remodelling of the endothelial monolayer, leading to the opening of the intercellular space. In this review, strategies used by the bacteria to survive in the bloodstream, to colonize the brain vasculature and to cross the blood-brain barrier will be discussed.

Published
2012

17. Meningococcus Hijacks a β2-Adrenoceptor/β-Arrestin Pathway to Cross Brain Microvasculature Endothelium

Author

Xavier Nassif, Mathieu Coureuil, Hervé Enslen, Mark G.H. Scott, Sandrine Bourdoulous, Cédric Boularan, Hervé Lécuyer, Stefano Marullo, Magali Soyer, and Guillain Mikaty

Subjects
Endothelium, Arrestins, Neisseria meningitidis, Biology, Blood–brain barrier, Cell junction, Bacterial Adhesion, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Receptors, Adrenergic, beta, Arrestin, medicine, Humans, beta-Arrestins, 030304 developmental biology, 0303 health sciences, Biochemistry, Genetics and Molecular Biology(all), Beta-Arrestins, Brain, Endothelial Cells, 3. Good health, Cell biology, Meningococcal Infections, medicine.anatomical_structure, Blood-Brain Barrier, Signal transduction, Tyrosine kinase, 030217 neurology & neurosurgery, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src
Abstract

SummaryFollowing pilus-mediated adhesion to human brain endothelial cells, meningococcus (N. meningitidis), the bacterium causing cerebrospinal meningitis, initiates signaling cascades, which eventually result in the opening of intercellular junctions, allowing meningeal colonization. The signaling receptor activated by the pathogen remained unknown. We report that N. meningitidis specifically stimulates a biased β2-adrenoceptor/β-arrestin signaling pathway in endothelial cells, which ultimately traps β-arrestin-interacting partners, such as the Src tyrosine kinase and junctional proteins, under bacterial colonies. Cytoskeletal reorganization mediated by β-arrestin-activated Src stabilizes bacterial adhesion to endothelial cells, whereas β-arrestin-dependent delocalization of junctional proteins results in anatomical gaps used by bacteria to penetrate into tissues. Activation of β-adrenoceptor endocytosis with specific agonists prevents signaling events downstream of N. meningitidis adhesion and inhibits bacterial crossing of the endothelial barrier. The identification of the mechanism used for hijacking host cell signaling machineries opens perspectives for treatment and prevention of meningococcal infection.PaperFlick

Published
2010

18. MmpS4 promotes glycopeptidolipids biosynthesis and export in Mycobacterium smegmatis

Author

Jean-Marc Reyrat, Daniel Euphrasie, Yossef Av-Gay, W. Sougakoff, Mamadou Daffé, Rodgoun Attarian, Mathieu Coureuil, Horacio Bach, Françoise Laval, Caroline Deshayes, and Gilles Etienne

Subjects
0303 health sciences, biology, Cell division, 030306 microbiology, Mycobacterium smegmatis, biology.organism_classification, Microbiology, Complementation, 03 medical and health sciences, chemistry.chemical_compound, Glycolipid, Biosynthesis, chemistry, Biochemistry, Membrane protein, Lipid biosynthesis, Molecular Biology, Gene, 030304 developmental biology
Abstract

Summary The MmpS family (mycobacterial membrane protein small) includes over 100 small membrane proteins specific to the genus Mycobacterium that have not yet been studied experimentally. The genes encoding MmpS proteins are often associated with mmpL genes, which are homologous to the RND (resistance nodulation cell division) genes of Gram-negative bacteria that encode proteins functioning as multidrug efflux system. We showed by molecular genetics and biochemical analysis that MmpS4 in Mycobacterium smegmatis is required for the production and export of large amounts of cell surface glycolipids, but is dispensable for biosynthesis per se. A new specific and sensitive method utilizing single-chain antibodies against the surface-exposed glycolipids was developed to confirm that MmpS4 was dispensable for transport to the surface. Orthologous complementation demonstrated that the MmpS4 proteins are exchangeable, thus not specific to a defined lipid species. MmpS4 function requires the formation of a protein complex at the pole of the bacillus, which requires the extracytosolic C-terminal domain of MmpS4. We suggest that MmpS proteins facilitate lipid biosynthesis by acting as a scaffold for coupled biosynthesis and transport machinery.

Published
2010

19. Meningococcal Type IV Pili Recruit the Polarity Complex to Cross the Brain Endothelium

Author

Xavier Nassif, Guillaume Duménil, Florence Miller, Mathieu Coureuil, Pierre-Olivier Couraud, Babette B. Weksler, Hervé Lécuyer, Christine Bernard, Ignacio A. Romero, Sandrine Bourdoulous, René-Marc Mège, Guillain Mikaty, INSERM U1002, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weill Medical College of Cornell University [New York], Department of Biological Sciences, The Open University [Milton Keynes] (OU), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), The Open University [Milton Keynes] ( OU ), and Coureuil, Mathieu

Subjects
MESH : Cell Line, Delta Catenin, Cell Cycle Proteins, blood brain barrier, Neisseria meningitidis, medicine.disease_cause, Cell junction, MESH : cdc42 GTP-Binding Protein, Bacterial Adhesion, MESH: Cadherins, MESH : Blood-Brain Barrier, MESH: Blood-Brain Barrier, MESH : Cell Cycle Proteins, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Cell polarity, MESH: Endothelial Cells, MESH : Adaptor Proteins, Signal Transducing, cdc42 GTP-Binding Protein, MESH: Antigens, CD, Protein Kinase C, 0303 health sciences, Multidisciplinary, Cell adhesion molecule, MESH : Fimbriae, Bacterial, Brain, Cell Polarity, meningitis, Catenins, Cadherins, endothelial cells, 3. Good health, Cell biology, Endothelial stem cell, Intercellular Junctions, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, Cdc42 GTP-Binding Protein, Blood-Brain Barrier, MESH : Intercellular Junctions, MESH: Cell Adhesion Molecules, MESH : Cadherins, MESH: Endothelium, Vascular, MESH: Membrane Proteins, MESH: Cell Polarity, MESH : Cell Polarity, MESH : Bacterial Adhesion, Biology, Blood–brain barrier, MESH: Phosphoproteins, Article, MESH: Neisseria meningitidis, MESH : Cell Adhesion Molecules, Cell Line, MESH: Fimbriae, Bacterial, MESH: Brain, 03 medical and health sciences, MESH: Cell Cycle Proteins, Antigens, CD, MESH : Antigens, CD, medicine, Humans, MESH : Protein Kinase C, MESH: Bacterial Adhesion, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Catenins, Adaptor Proteins, Signal Transducing, MESH: Adaptor Proteins, Signal Transducing, 030304 developmental biology, MESH: Humans, MESH: cdc42 GTP-Binding Protein, MESH : Endothelial Cells, MESH : Neisseria meningitidis, Cadherin, MESH : Humans, Membrane Proteins, Phosphoproteins, MESH: Protein Kinase C, MESH : Catenins, MESH: Cell Line, MESH : Brain, MESH : Endothelium, Vascular, MESH : Membrane Proteins, Fimbriae, Bacterial, Endothelium, Vascular, MESH : Phosphoproteins, Cell Adhesion Molecules, 030217 neurology & neurosurgery, MESH: Intercellular Junctions
Abstract

Breaking the Barrier Being able to deliver drugs into the brain to treat degenerative diseases such as Alzheimer's or Parkinson's requires the ability to traverse the blood-brain barrier (BBB). Understanding the formation of the very specific adherent junctions (AJ) and tight junctions present at the BBB cell junctions is a prerequisite to the design of such therapeutics. However, diminishing the expression of any one component involved in the formation of these intercellular junctions destroys them. Coureuil et al. (p. 83 , published online 11 June) exploited the specific recruitment of AJ proteins by Neisseria meningitidis to dissect this process. Adhesion of the bacteria to human brain endothelial cells recruited the polarity complex Par3/Par6/PKCζ required for the establishment of eukaryotic cell polarity and the formation of intercellular junctions. The bacterial recruitment of the polarity complex depleted junctional proteins at the cell-cell interface opening the intercellular junctions at the brainendothelial interface.

Published
2009

20. The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation

Author

Terry Brissac, Xavier Nassif, Ghislaine Lioux, Gilles Phan, Coralie Bouchiat, Florence Miller, Mathieu Coureuil, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Coureuil, Mathieu

Subjects
Neisseria meningitidis, medicine.disease_cause, Microbiology, Pilus, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Antigenic variation, Cell Adhesion, Humans, Secretion, Cell adhesion, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Cells, Cultured, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Natural competence, Endothelial Cells, Epithelial Cells, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Antigenic Variation, QR1-502, 3. Good health, Transformation (genetics), [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pilin, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, biology.protein, Mutant Proteins, Fimbriae Proteins, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Research Article
Abstract

Type IV pili (Tfp) are expressed by many Gram-negative bacteria to promote aggregation, adhesion, internalization, twitching motility, or natural transformation. Tfp of Neisseria meningitidis, the causative agent of cerebrospinal meningitis, are involved in the colonization of human nasopharynx. After invasion of the bloodstream, Tfp allow adhesion of N. meningitidis to human endothelial cells, which leads to the opening of the blood-brain barrier and meningitis. To achieve firm adhesion, N. meningitidis induces a host cell response that results in elongation of microvilli surrounding the meningococcal colony. Here we study the role of the major pilin subunit PilE during host cell response using human dermal microvascular endothelial cells and the pharynx carcinoma-derived FaDu epithelial cell line. We first show that some PilE variants are unable to induce a host cell response. By engineering PilE mutants, we observed that the PilE C-terminus domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and that hypervariable regions confer different host cell specificities. Moreover, the study of point mutants of the pilin D-region combined with structural modeling of PilE revealed that the D-region contains two independent regions involved in signaling to human dermal microvascular endothelial cells (HDMECs) or FaDu cells. Our results indicate that the diversity of the PilE D-region sequence allows the induction of the host cell response via several receptors. This suggests that Neisseria meningitidis has evolved a powerful tool to adapt easily to many niches by modifying its ability to interact with host cells., IMPORTANCE Type IV pili (Tfp) are long appendages expressed by many Gram-negative bacteria, including Neisseria meningitidis, the causative agent of cerebrospinal meningitis. These pili are involved in many aspects of pathogenesis: natural competence, aggregation, adhesion, and twitching motility. More specifically, Neisseria meningitidis, which is devoid of a secretion system to manipulate its host, has evolved its Tfp to signal to brain endothelial cells and open the blood-brain barrier. In this report, we investigate, at the molecular level, the involvement of the major pilin subunit PilE in host cell response. Our results indicate that the PilE C-terminal domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and contains two independent regions involved in host cell signaling.

Published
2014

21. Arrestins in host-pathogen interactions

Author

Stefano Marullo, Mathieu Coureuil, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), U1002, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Marullo, Stefano, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Scaffold protein, Innate immune response, MESH: Signal Transduction, Arrestins, sepsis, 0302 clinical medicine, MESH: Animals, Toll-­‐Like Receptors, Receptor, MESH : Host-Pathogen Interactions, Organism, beta-Arrestins, 0303 health sciences, MESH : Viruses, MESH : Immunity, Innate, 3. Good health, Cell biology, meningococcus, Host-Pathogen Interactions, Viruses, MESH: Immunity, Innate, MESH: Arrestins, Signal transduction, NF-­‐κB, pneumococcus, Signal Transduction, blood-­‐brain barrier, MESH : Arrestins, Context (language use), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, MESH: Viruses, 03 medical and health sciences, Immunity, Animals, Humans, MESH : Bacteria, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, MESH : Signal Transduction, Innate immune system, MESH: Humans, Bacteria, Beta-Arrestins, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Humans, MESH: Host-Pathogen Interactions, anthrax, Filoviridae, Immunity, Innate, MESH: Bacteria, Immunology, HTLV-­‐1, MESH : Animals, 030217 neurology & neurosurgery
Abstract

International audience; In the context of host-pathogen interaction, host cell receptors and signaling pathways are essential for both invading pathogens, which exploit them for their own profit, and the defending organism, which activates early mechanism of defense, known as innate immunity, to block the aggression. Because of their central role as scaffolding proteins downstream of activated receptors, β-arrestins are involved in multiple signaling pathways activated in host cells by pathogens. Some of these pathways participate in the innate immunity and the inflammatory response. Other β-arrestin-dependent pathways are actually hijacked by microbes and toxins to penetrate into host cells and spread in the organism.

Published
2014

22. Chronic Meningococcemia Cutaneous Lesions Involve Meningococcal Perivascular Invasion Through the Remodeling of Endothelial Barriers

Author

Marie-Cécile Vacher-Lavenu, Mathieu Coureuil, Hervé Lécuyer, Johan Chanal, Claire Poyart, Xavier Nassif, Muhamed-Kheir Taha, Philippe Morand, Nicolas Dupin, Agnès Carlotti, Alain Schmitt, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Pathogénie des infections systémiques (Inserm U1002), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Infections Bactériennes Invasives, Institut Pasteur [Paris] (IP), This work was supported by Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur, and Institut Cochin. The laboratory of X. N. is supported by INSERM, Université Paris Descartes, Agence Nationale de la Recherche, and Fondation pour la Recherche Médicale. The laboratory of M. K. T. is supported by Institut Pasteur and the Department of Health., Université Paris Descartes - Paris 5 (UPD5)-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 Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], and CHU Cochin [AP-HP]

Subjects
Microbiology (medical), Pathology, medicine.medical_specialty, MESH: Skin Diseases, Bacterial, Endothelium, endothelium, skin lesion, Bacteremia, MESH: Endothelium, medicine.disease_cause, Meningococcal disease, MESH: Meningococcal Infections, Sepsis, sepsis, 03 medical and health sciences, neisseria meningitidis, In vivo, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Compartment (pharmacokinetics), MESH: Bacteremia, 030304 developmental biology, drug administration routes, 0303 health sciences, 030306 microbiology, business.industry, Neisseria meningitidis, MESH: Chronic Disease, Skin Diseases, Bacterial, medicine.disease, Chronic meningococcemia, 3. Good health, Peripheral, Meningococcal Infections, chronic, Infectious Diseases, medicine.anatomical_structure, Chronic Disease, Immunology, meningococcemia, blood capillaries, business, dislocations
Abstract

International audience; Chronic meningococcemia is a form of sepsis with frequent polymorphous skin lesions. Both in vivo and in vitro data suggest that, in these lesions, meningococci gain access from the capillary lumen to the peripheral extravascular compartment, in the absence of vascular dislocation, through a paraendothelial route.

Published
2012

23. Mouse differentiating spermatogonia can generate germinal stem cells in vivo

Author

Isabelle Allemand, Lydia Riou, Florence Le Page, Jacques Testart, Pierre Fouchet, Vilma Barroca, Mathieu Coureuil, J.-P. Louis, Bruno Lassalle, Gametogenèse et génotoxicité (UMR_S_566 ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-IFR13-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Transgene, Green Fluorescent Proteins, Mice, Transgenic, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Testis, Glial cell line-derived neurotrophic factor, Animals, Regeneration, Cell Lineage, Glial Cell Line-Derived Neurotrophic Factor, Progenitor cell, Cell Proliferation, 030304 developmental biology, Stem cell transplantation for articular cartilage repair, 0303 health sciences, Stem Cells, fungi, food and beverages, Cell Differentiation, Cell Biology, Cell Dedifferentiation, Spermatogonia, Cell biology, Mice, Inbred C57BL, Endothelial stem cell, Haematopoiesis, Germ Cells, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Fibroblast Growth Factor 2, Stem cell, 030217 neurology & neurosurgery, Stem Cell Transplantation, Adult stem cell
Abstract

International audience; In adults, stem cells are responsible for the maintenance of many actively renewing tissues, such as haematopoietic, skin, gut and germinal tissues. These stem cells can self-renew or be committed to becoming progenitors. Stem-cell commitment is thought to be irreversible but in male and female Drosophila melanogaster, it was shown recently that differentiating germ cells can revert to functional stem cells that can restore germinal lineage. Whether progenitors are also able to generate stem cells in mammals remains unknown. Here we show that purified mouse spermatogonial progenitors committed to differentiation can generate functional germinal stem cells that can repopulate germ-cell-depleted testes when transplanted into adult mice. We found that GDNF, a key regulator of the stem-cell niche, and FGF2 are able to reprogram in vitro spermatogonial progenitors for reverse differentiation. This study supports the emerging concept that the stem-cell identity is not restricted in adults to a definite pool of cells that self-renew, but that stemness could be acquired by differentiating progenitors after tissue injury and throughout life.

Published
2009

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