Search

Your search keyword '"Sciences du Vivant [q-bio]/Microbiologie et Parasitologie"' showing total 46 results
Start Over Descriptor "Sciences du Vivant [q-bio]/Microbiologie et Parasitologie"
46 results on '"Sciences du Vivant [q-bio]/Microbiologie et Parasitologie"'

1. Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study

Author

François Danion, Céline Duval, François Séverac, Philippe Bachellier, Ermanno Candolfi, Vincent Castelain, Raphaël Clere-Jehl, Julie Denis, Laurence Dillenseger, Eric Epailly, Justine Gantzer, Blandine Guffroy, Yves Hansmann, Jean-Etienne Herbrecht, Valérie Letscher-Bru, Pierre Leyendecker, Pauline Le Van Quyen, Pierre-Olivier Ludes, Guillaume Morel, Bruno Moulin, Catherine Paillard, Benjamin Renaud-Picard, Anne-Claude Roche, Marcela Sabou, Francis Schneider, Morgane Solis, Emilie Talagrand-Reboul, Francis Veillon, Marie-Pierre Ledoux, Célestine Simand, Raoul Herbrecht, Pietro Francesco Addeo, Dominique Astruc, Mathieu Baldacini, Karin Bilger, Marie-Pierrette Chenard, Olivier Collange, Tristan Degot, Nadia Dhif, Elise Dicop, Samira Fafi-Kremer, Luc-Matthieu Fornecker, Charline Fuseau, Max Guillot, Mary-Line Harlay, Ralf Janssen-Langenstein, Benoît Jaulhac, Charlotte Kaeuffer, Romain Kessler, Christine Kummerlen, Annegret Laplace, Anne Launoy, Bruno Lioure, Hamid Merdji, Paul-Michel Mertes, Shanti Natarajan-Ame, Gabriel Nisand, Michele Porzio, Julien Pottecher, Maleka Schenck-Dhif, Cécile Sonntag, Elise Toussaint, Anne Zilliox, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Cancérologie de Strasbourg Europe (ICANS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions Hôte pathogène, Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nanomédecine Régénérative (NanoRegMed), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte

Subjects
0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Coinfections, Computed tomography, Aspergillosis, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Invasive fungal infections, Internal medicine, medicine, Humans, Leukaemia, 030212 general & internal medicine, Mortality, Child, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, Retrospective Studies, Aspergillus species, Aged, 80 and over, medicine.diagnostic_test, business.industry, Coinfection, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, medicine.disease, 3. Good health, Transplantation, Infectious Diseases, Fungal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Risk factors, Child, Preschool, Hematologic Neoplasms, business
Abstract

Objectives To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. Patients and methods We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. Results Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8–43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2–4.4)), other haematological malignancies (OR 2.1 (1.2–3.8)), other underlying diseases (OR 4.3 (1.4–13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2–3.0)), fever (OR 2.4 (1.5–4.1)), tracheal intubation (OR 2.6 (1.5–4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1–6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3–3.7) and OR 2.2 (1.2–4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1–1.9), p Conclusions Coinfections are frequent in IA patients and are associated with higher mortality.

Published
2021

2. Water table fluctuations affect dichloromethane biodegradation in lab-scale aquifers contaminated with organohalides

Author

Jérémy Masbou, Benjamin Belfort, Gwenaël Imfeld, Emilie E. L. Muller, Stéphane Vuilleumier, Maria Prieto-Espinoza, Sylvain Weill, François Lehmann, Institut Terre Environnement Strasbourg (ITES), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire, génomique, microbiologie (GMGM), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Environmental Engineering, 010504 meteorology & atmospheric sciences, Water table, DCM degradation, Aquifer, dynamic conditions, 010501 environmental sciences, 01 natural sciences, Bioremediation, Desulfosporosinus, cardiovascular diseases, 16S rRNA, Planète et Univers [physics]/Sciences de la Terre, Groundwater, Waste Management and Disposal, 0105 earth and related environmental sciences, Water Science and Technology, Civil and Structural Engineering, Carbon Isotopes, Methylene Chloride, geography, geography.geographical_feature_category, biology, Stable isotope ratio, Chemistry, Ecological Modeling, Biodegradation, biology.organism_classification, musculoskeletal system, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Pollution, Anoxic waters, 6. Clean water, Biodegradation, Environmental, 13. Climate action, Environmental chemistry, laboratory aquifers, [SDE]Environmental Sciences, cardiovascular system, Laboratories, [CHIM.OTHE]Chemical Sciences/Other, Water Pollutants, Chemical, multi-element CSIA
Abstract

Dichloromethane (DCM) is a toxic industrial solvent frequently detected in multi-contaminated aquifers. It can be degraded biotically or abiotically, and under oxic or anoxic conditions. The extent and pathways of DCM degradation in aquifers may thus depend on water table fluctuations and microbial responses to hydrochemical variations. Here, we examined the effect of water table fluctuations on DCM biodegradation in two laboratory aquifers fed with O2-depleted DCM-spiked groundwater from a well-characterized former industrial site. Hydrochemistry, stable isotopes of DCM (δ13C and δ37Cl), and bacterial community composition were examined to determine DCM mass removal and degradation pathways under steady-state (static water table) and transient (fluctuating water table) conditions. DCM mass removal was more pronounced under transient (95%) than under steady-state conditions (42%). C and Cl isotopic fractionation values were larger under steady-state ( e bulk C = −23.6 ± 3.2‰, and e bulk Cl = −8.7 ± 1.6‰) than under transient conditions ( e bulk C = −11.8 ± 2.0‰, and e bulk Cl = −3.1 ± 0.6‰). Dual C-Cl isotope analysis suggested the prevalence of distinct anaerobic DCM degradation pathways, with ΛC/Cl values of 1.92 ± 0.30 and 3.58 ± 0.42 under steady-state and transient conditions, respectively. Water table fluctuations caused changes in redox conditions and oxygen levels, resulting in a higher relative abundance of Desulfosporosinus (Peptococcaceae family). Taken together, our results show that water table fluctuations enhanced DCM biodegradation, and correlated with bacterial taxa associated with anaerobic DCM degradation. Our integrative approach allows to evaluate anaerobic DCM degradation under dynamic hydrogeological conditions, and may help improving bioremediation strategies at DCM contaminated sites.

Published
2021

3. Comparative Study of Secreted Proteins, Enzymatic Activities of Wood Degradation and Stilbene Metabolization in Grapevine Botryosphaeria Dieback Fungi

Author

Clément Labois, Elodie Stempien, Justine Schneider, Christine Schaeffer-Reiss, Christophe Bertsch, Mary-Lorène Goddard, Julie Chong, Laboratoire Vigne Biotechnologie et Environnement (LVBE), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Laboratoire d'innovation moléculaire et applications (LIMA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Botryosphaeriaceae, stilbene metabolization, QH301-705.5, fungi, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Article, grapevine, secreted proteins, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Botryosphaeriaceae, Biology (General), [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Chimie/Chimie analytique
Abstract

Botryosphaeriaceae fungi are plant pathogens associated with Botryosphaeria dieback. To better understand the virulence factors of these fungi, we investigated the diversity of secreted proteins and extracellular enzyme activities involved in wood degradation and stilbene metabolization in Neofusicoccum&nbsp, parvum and Diplodia&nbsp, seriata, which are two major fungi associated with grapevine B. dieback. Regarding the analysis of proteins secreted by the two fungi, our study revealed that N. parvum, known to be more aggressive than D. seriata, was characterized by a higher quantity and diversity of secreted proteins, especially hydrolases and oxidoreductases that are likely involved in cell wall and lignin degradation. In addition, when fungi were grown with wood powder, the extracellular laccase and Mn peroxidase enzyme activities were significantly higher in D. seriata compared to N. parvum. Importantly, our work also showed that secreted Botryosphaeriaceae proteins produced after grapevine wood addition are able to rapidly metabolize the grapevine stilbenes. Overall, a higher diversity of resveratrol and piceatannol metabolization products was found with enzymes of N. parvum compared to D. seriata. This study emphasizes the diversity of secreted virulence factors found in B. dieback fungi and suggests that some resveratrol oligomers produced in grapevine wood after pathogen attack could be formed via pathogenic fungal oxidases.

Published
2021

4. Negative Impact of Citral on Susceptibility of Pseudomonas aeruginosa to Antibiotics

Author

Alexandre Tetard, Sarah Foley, Gaëtan L. A. Mislin, Jean-Michel Brunel, Estefania Oliva, Freddy Torrealba Anzola, Andy Zedet, Bruno Cardey, Yann Pellequer, Christophe Ramseyer, Patrick Plésiat, Catherine Llanes, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), Laboratoire de Glycochimie, des Antimicrobiens et des Agro-ressources - UMR CNRS 7378 (LG2A ), Université de Picardie Jules Verne (UPJV)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pathologies et épithéliums : prévention, innovation, traitements, évaluation (EA 4267) (PEPITE), Université de Franche-Comté (UFC), Laboratoire Chrono-environnement (UMR 6249) (LCE), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Pathologies et épithéliums : prévention, innovation, traitements, évaluation (UR 4267) (PEPITE), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), and Brunel, Jean Michel

Subjects
0301 basic medicine, Microbiology (medical), antibiotic resistance, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibiotics, medicine.disease_cause, Citral, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, tobramycin-citral Schiff base, Tobramycin, medicine, [CHIM]Chemical Sciences, essential oils, citral, Original Research, Pseudomonas aeruginosa, Chemistry, Aminoglycoside, colistin-citral Schiff base, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, efflux, QR1-502, 3. Good health, 030104 developmental biology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Colistin, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Gentamicin, Efflux, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.drug
Abstract

Essential oils (EOs) or their components are widely used by inhalation or nebulization to fight mild respiratory bacterial infections. However, their interaction with antibiotics is poorly known. In this study we evaluated the effects of citral, the main component of lemongrass oil, on in vitro susceptibility of Pseudomonas aeruginosa to antibiotics. Exposure of strain PA14 to subinhibitory concentrations of citral increased expression of operons encoding the multidrug efflux systems MexEF-OprN and MexXY/OprM, and bacterial resistance to anti-pseudomonal antibiotics including imipenem (twofold), gentamicin (eightfold), tobramycin (eightfold), ciprofloxacin (twofold), and colistin (≥128-fold). Use of pump deletion mutants showed that in addition to efflux other mechanisms were involved in this citral-induced phenotype. Determination of Zeta potential suggested that citral impairs the cell surface binding of aminoglycosides and colistin used at low concentrations (≤10 μg/mL). Moreover, experiments based on Raman spectroscopy and high-resolution mass spectrometry demonstrated formation of a Schiff base between the aldehyde group of citral and amino-groups of tobramycin and colistin. Chemical synthesis of tobracitryl, the imine compound resulting from condensation of citral and tobramycin, confirmed the loss of antibiotic activity due to adduct formation. Altogether these data point to the potential risk concern of self-medication with EOs containing citral in patients suffering from P. aeruginosa chronic lung infections and being treated with aerosols of aminoglycoside or colistin.

Published
2021

5. Efficient Reduction of Iron Oxides byPaenibacillusspp. Strains Isolated from Tropical Soils

Author

Stéphanie Loyaux-Lawniczak, Stéphane Vuilleumier, Valérie A. Geoffroy, Laboratoire d'Hydrologie et de Géochimie de Strasbourg (LHyGeS), Ecole et Observatoire des Sciences de la Terre (EOST), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire, génomique, microbiologie (GMGM), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Goethite, 030106 microbiology, chemistry.chemical_element, Manganese, 010501 environmental sciences, Direct reduced iron, 01 natural sciences, Microbiology, Ferrous, Metal, 03 medical and health sciences, Paenibacillus, Ferrihydrite, Iron bacteria, Earth and Planetary Sciences (miscellaneous), Environmental Chemistry, 0105 earth and related environmental sciences, General Environmental Science, biology, food and beverages, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, biology.organism_classification, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Environmental chemistry, visual_art, visual_art.visual_art_medium
Abstract

The genus Paenibacillus was hardly described as a Fe(III)-reducing agent, only limited to reduce soluble forms or Fe inserted in poorly crystallized structures. In this study, three Paenibacillus strains capable of reducing manganese oxides in addition to iron oxides were isolated from Cameroonian and Brazilian soils. These strains reduced iron minerals from poorly crystallized 2-line ferrihydrite to well-crystallized Al-substituted and pure goethite with a significant production of soluble ferrous iron. These Paenibacillus strains, inhabitants from ferralitic temporarily waterlogged soils, could play an important role in the bioweathering of minerals and metal mobility in soils.

Published
2019

6. Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials

Author

Lefeuvre, Bastien, Cantero, Paola, Ehret-Sabatier, Laurence, Lenormand, Cedric, Barthel, Cathy, Po, Chrystelle, Parveen, Nikhat, Grillon, Antoine, Jaulhac, Benoit, Boulanger, Nathalie, Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Gaillard, Brigitte, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE17-0003,DIABOLYC,Diagnostic cutané de la borréliose de Lyme tardive(2016)

Subjects
Lyme Disease, Bacteria, [SDV]Life Sciences [q-bio], Infectious-disease diagnostics, lcsh:R, Aucun, Lidocaine, lcsh:Medicine, Diseases, bacterial infections and mycoses, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Microbiology, Article, [SDV] Life Sciences [q-bio], Mice, Borrelia burgdorferi Group, Adrenal Cortex Hormones, Borrelia burgdorferi, Animals, Infectious diseases, lcsh:Q, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Skin
Abstract

International audience; Lyme borreliosis is the most prevalent vector-borne disease in northern hemisphere. Borrelia burgdorferi sensu lato spirochetes are transmitted by Ixodes species ticks. During a blood meal, these spirochetes are inoculated into the skin where they multiply and often spread to various target organs: disseminated skin sites, the central nervous system, the heart and large joints. The usual diagnosis of this disease relies on serological tests. However, in patients presenting persistent clinical manifestations, this indirect diagnosis is not capable of detecting an active infection. If the serological tests are positive, it only proves that exposure of an individual to Lyme spirochetes had occurred. Although culture and quantitative PCR detect active infection, currently used tests are not sensitive enough for wide-ranging applications. Animal models have shown that B. burgdorferi persists in the skin. We present here our targeted proteomics results using infected mouse skin biopsies that facilitate detection of this pathogen. We have employed several novel approaches in this study. First, the effect of lidocaine, a local anesthetic used for human skin biopsy, on B. burgdorferi presence was measured. We further determined the impact of topical corticosteroids to reactivate Borrelia locally in the skin. This local immunosuppressive compound helps follow-up detection of spirochetes by proteomic analysis of Borrelia present in the skin. This approach could be developed as a novel diagnostic test for active Lyme borreliosis in patients presenting disseminated persistent infection. Although our results using topical corticosteroids in mice are highly promising for recovery of spirochetes, further optimization will be needed to translate this strategy for diagnosis of Lyme disease in patients.

Published
2020

7. Proteomic as an Exploratory Approach to Develop Vaccines Against Tick-Borne Diseases Using Lyme Borreliosis as a Test Case

Author

Talagrand-Reboul, E., Westermann, B., Raess M., A., Schnell, G., Cantero, P., Barthel, C., Ehret-Sabatier, Laurence, JAULHAC, B., Boulanger, N., Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
skin, proteomics, tick-borne diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Borrelia, lcsh:R, lcsh:Medicine, Lyme, markers of infection, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Article
Abstract

International audience; Tick-borne diseases affecting humans and animals are on the rise worldwide. Vaccines constitute an effective control measure, but very few are available. We selected Lyme borreliosis, a bacterial infection transmitted by the hard tick Ixodes, to validate a new concept to identify vaccine candidates. This disease is the most common tick-borne disease in the Northern Hemisphere. Although attempts to develop a vaccine exist, none have been successfully marketed. In tick-borne diseases, the skin constitutes a very specific environment encountered by the pathogen during its co-inoculation with tick saliva. In a mouse model, we developed a proteomic approach to identify vaccine candidates in skin biopsies. We identified 30 bacterial proteins after syringe inoculation or tick inoculation of bacteria. Discovery proteomics using mass spectrometry might be used in various tick-borne diseases to identify pathogen proteins with early skin expression. It should help to better develop sub-unit vaccines based on a cocktail of several antigens, associated with effective adjuvant and delivery systems of antigens. In all vector-borne diseases, the skin deserves further investigation to better define its role in the elaboration of protective immunity against pathogens.

Published
2020
Full Text
View/download PDF

8. Pyocin S5 import into Pseudomonas aeruginosa reveals a generic mode of bacteriocin transport

Author

Behrens, Hannah M., Lowe, Edward D., Gault, J. (Joseph), Housden, Nicholas G., Kaminska, R. (Renata), Weber, T. Moritz, Thompson, Catriona M. A., Mislin, G. (Gaetan), Schalk, I. (Isabelle), Walker, D. (Daniel), Robinson, Carol V., Kleanthous, C. (Colin), Cossart, Pascale F. (editor), Department of Biochemistry [Oxford], University of Oxford [Oxford], Chemistry Research Laboratory [Oxford, UK], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Institute of Infection, Immunity & Inflammation, University of Glasgow, Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Molecular Biology and Physiology, medicine.disease_cause, Microbiology, 03 medical and health sciences, Bacteriocin, Virology, medicine, Inner membrane, pyocin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Escherichia coli, membrane, 030304 developmental biology, Pyocins, 0303 health sciences, biology, Pseudomonas aeruginosa, Chemistry, 030306 microbiology, Cell Membrane, Membrane Transport Proteins, Biological Transport, Transporter, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR1-502, Cell biology, transport, Bacterial outer membrane, Bacteriocin transport, Bacteria, Research Article, Bacterial Outer Membrane Proteins
Abstract

Bacteriocins are toxic polypeptides made by bacteria to kill their competitors, making them interesting as potential antibiotics. Here, we reveal unsuspected commonalities in bacteriocin uptake pathways, through molecular and cellular dissection of the import pathway for the pore-forming bacteriocin pyocin S5 (PyoS5), which targets Pseudomonas aeruginosa. In addition to its C-terminal pore-forming domain, PyoS5 is composed of two tandemly repeated helical domains that we also identify in other pyocins. Functional analyses demonstrate that they have distinct roles in the import process. One recognizes conserved sugars projected from the surface, while the other recognizes a specific outer membrane siderophore transporter, FptA, in the case of PyoS5. Through engineering of Escherichia coli cells, we show that pyocins can be readily repurposed to kill other species. This suggests basic ground rules for the outer membrane translocation step that likely apply to many bacteriocins targeting Gram-negative bacteria., Pyocin S5 (PyoS5) is a potent protein bacteriocin that eradicates the human pathogen Pseudomonas aeruginosa in animal infection models, but its import mechanism is poorly understood. Here, using crystallography, biophysical and biochemical analyses, and live-cell imaging, we define the entry process of PyoS5 and reveal links to the transport mechanisms of other bacteriocins. In addition to its C-terminal pore-forming domain, elongated PyoS5 comprises two novel tandemly repeated kinked 3-helix bundle domains that structure-based alignments identify as key import domains in other pyocins. The central domain binds the lipid-bound common polysaccharide antigen, allowing the pyocin to accumulate on the cell surface. The N-terminal domain binds the ferric pyochelin transporter FptA while its associated disordered region binds the inner membrane protein TonB1, which together drive import of the bacteriocin across the outer membrane. Finally, we identify the minimal requirements for sensitizing Escherichia coli toward PyoS5, as well as other pyocins, and suggest that a generic pathway likely underpins the import of all TonB-dependent bacteriocins across the outer membrane of Gram-negative bacteria.

Published
2020

9. Iron acquisition in Pseudomonas aeruginosa by the siderophore pyoverdine: an intricate interacting network including periplasmic and membrane proteins

Author

Béatrice Roche, Isabelle J. Schalk, Anne Bonneau, Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
0301 basic medicine, Siderophore, Iron, 030106 microbiology, Protein domain, lcsh:Medicine, Siderophores, medicine.disease_cause, Article, 03 medical and health sciences, chemistry.chemical_compound, Protein Domains, Metalloproteins, medicine, Secretion, lcsh:Science, Cellular microbiology, Ion transport, Multidisciplinary, Pyoverdine, Pseudomonas aeruginosa, Chemistry, lcsh:R, Membrane Proteins, Biological Transport, Periplasmic space, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, Biochemistry, Membrane protein, Periplasm, lcsh:Q, Bacterial outer membrane, Oligopeptides
Abstract

Pyoverdine (PVDI) has been reported to act both as a siderophore for scavenging iron (a key nutrient) and a signaling molecule for the expression of virulence factors. This compound is itself part of a core set of virulence factors produced by Pseudomonas aeruginosa during infections. Once secreted into the bacterial environment and having scavenged ferric iron, PVDI-Fe3+ is taken back into the P. aeruginosa periplasm via the outer membrane transporters FpvAI and FpvB. Iron release from PVDI in the bacterial periplasm involves numerous proteins encoded by the fpvGHJKCDEF genes and a mechanism of iron reduction. Here, we investigated the global interacting network between these various proteins using systematic bacterial two-hybrid screening. We deciphered a network of five interacting proteins composed of two inner-membrane proteins, FpvG (iron reductase) and FpvH (unknown function), and three periplasmic proteins, FpvJ (unknown function), FpvF (periplasmic PVDI-binding protein), and FpvC (iron periplasmic-binding protein). This interacting network strongly suggests the existence of a large protein machinery composed of these five proteins, all playing a role in iron acquisition by PVDI. Furthermore, we discovered an interaction between the periplasmic siderophore binding protein FpvF and the PvdRT-OpmQ efflux pump, also suggesting a role for FpvF in apo-PVDI recycling and secretion after iron delivery. These results highlight a multi-protein complex that drives iron release from PVDI in the periplasm of P. aeruginosa.

Published
2020

10. Virulence of beta-hemolytic streptococci in infective endocarditis

Author

Yves Hansmann, Xavier Argemi, A. Martin, N. Douiri, Yvon Ruch, Nicolas Lefebvre, Philippe Riegel, Jean-Philippe Mazzucotelli, Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), univOAK, Archive ouverte, and CHU Strasbourg

Subjects
Male, 0301 basic medicine, Staphylococcus, Aucun, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, Aged, 80 and over, Virulence, Streptococci, General Medicine, Middle Aged, Staphylococcal Infections, Cardiac surgery, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Beta-hemolytic, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infective endocarditis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Gentamicin, France, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Young Adult, 03 medical and health sciences, Early surgery, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Streptococcal Infections, Internal medicine, medicine, Humans, Gram-Positive Bacterial Infections, Aged, Retrospective Studies, Septic shock, business.industry, Streptococcus, Retrospective cohort study, Endocarditis, Bacterial, medicine.disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Morbidity, business, Enterococcus
Abstract

BACKGROUND: Streptococci involved in infective endocarditis (IE) primarily comprise alpha- or non-hemolytic streptococci (ANHS). Moreover, beta-hemolytic streptococci (BHS) can be involved, and guidelines recommend the addition of gentamicin for the first 2 weeks of treatment and the consideration of early surgery in such cases. This study compared the morbidity and mortality associated with IE depending on the microorganisms involved (BHS, ANHS, staphylococci, and enterococci). METHODS: We conducted a retrospective observational study between 2012 and 2017 in a single hospital in France. The endpoints were overall in-hospital mortality, 1-year mortality and the occurrence of complications. RESULTS: We analyzed 316 episodes of definite IE including 150 (38%), 96 (25%), 46 (12%), and 24 cases (6%) of staphylococcal, ANHS, enterococcal, and BHS IE, respectively. In-hospital mortality was significantly higher in the staphylococcal (n = 40; 26.7%) and BHS groups (n = 6; 25.0%) than in the ANHS (n = 9; 9.4%) and enterococcal groups (n = 5; 10.9%) (all p

Published
2020

11. Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms

Author

Isabelle J. Schalk, Philippe Hammann, Paola Cantero, Quentin Perraud, Vincent Normant, Véronique Gasser, Laurence Ehret-Sabatier, Gaëtan L. A. Mislin, Lauriane Kuhn, Béatrice Roche, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Siderophore, siderophore, Transcription, Genetic, Virulence Factors, Iron, Microorganism, Catechols, Siderophores, Iron Chelating Agents, medicine.disease_cause, Biochemistry, phenotypic plasticity, Microbiology, Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Pseudomonas, medicine, Label-free quantification, Humans, [CHIM]Chemical Sciences, Molecular Biology, TonB transporters, 030304 developmental biology, 0303 health sciences, Phenotypic plasticity, Pyoverdine, biology, Pseudomonas aeruginosa, Research, 030302 biochemistry & molecular biology, Biological Transport, Epithelial Cells, Gene Expression Regulation, Bacterial, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Adaptation, Physiological, Phenotype, chemistry, A549 Cells, Molecular biology, iron homeostasis, Pathogens, Bacteria
Abstract

International audience; Bacteria secrete siderophores to access iron, a key nutrient poorly bioavailable and the source of strong competition between microorganisms in most biotopes. Many bacteria also use siderophores produced by other microorganisms (exosiderophores) in a piracy strategy. Pseudomonas aeruginosa, an opportunistic pathogen, produces two siderophores, pyoverdine and pyochelin, and is also able to use a panel of exosiderophores. We first investigated expression of the various iron-uptake pathways of P. aeruginosa in three different growth media using proteomic and RT-qPCR approaches and observed three different phenotypic patterns, indicating complex phenotypic plasticity in the expression of the various iron-uptake pathways. We then investigated the phenotypic plasticity of iron-uptake pathway expression in the presence of various exosiderophores (present individually or as a mixture) under planktonic growth conditions, as well as in an epithelial cell infection assay. In all growth conditions tested, catechol-type exosiderophores were clearly more efficient in inducing the expression of their corresponding transporters than the others, showing that bacteria opt for the use of catechol siderophores to access iron when they are present in the environment. In parallel, expression of the proteins of the pyochelin pathway was significantly repressed under most conditions tested, as well as that of proteins of the pyoverdine pathway, but to a lesser extent. There was no effect on the expression of the heme and ferrous uptake pathways. Overall, these data provide precise insights on how P. aeruginosa adjusts the expression of its various iron-uptake pathways (phenotypic plasticity and switching) to match varying levels of iron and competition.

Published
2020

12. A Key Role for the Periplasmic PfeE Esterase in Iron Acquisition via the Siderophore Enterobactin in Pseudomonas aeruginosa

Author

Lucile Moynié, Julien Godet, Véronique Gasser, Françoise Hoegy, Mathilde Munier, Yves Mély, Gaëtan L. A. Mislin, Quentin Perraud, Isabelle J. Schalk, James H. Naismith, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, 0301 basic medicine, Siderophore, Protein Conformation, Iron, education, 030106 microbiology, Mutant, Siderophores, Crystallography, X-Ray, medicine.disease_cause, Biochemistry, Esterase, Enterobactin, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, otorhinolaryngologic diseases, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Pseudomonas Infections, Escherichia coli, ComputingMilieux_MISCELLANEOUS, Binding Sites, Chemistry, Hydrolysis, Esterases, General Medicine, Periplasmic space, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Enzyme binding, 030104 developmental biology, Pseudomonas aeruginosa, Molecular Medicine, Bacterial outer membrane
Abstract

Enterobactin (ENT) is a siderophore (iron-chelating compound) produced by Escherichia coli to gain access to iron, an indispensable nutrient for bacterial growth. ENT is used as an exosiderophore by Pseudomonas aeruginosa with transport of ferri-ENT across the outer membrane by the PfeA transporter. Next to the pfeA gene on the chromosome is localized a gene encoding for an esterase, PfeE, whose transcription is regulated, as for pfeA, by the presence of ENT in bacterial environment. Purified PfeE hydrolyzed ferri-ENT into three molecules of 2,3-DHBS (2,3-dihydroxybenzoylserine) still complexed with ferric iron, and complete dissociation of iron from ENT chelating groups was only possible in the presence of both PfeE and an iron reducer, such as DTT. The crystal structure of PfeE and an inactive PfeE mutant complexed with ferri-ENT or a nonhydrolyzable ferri-catechol complex allowed identification of the enzyme binding site and the catalytic triad. Finally, cell fractionation and fluorescence microscopy showed periplasmic localization of PfeE in P. aeruginosa cells. Thus, the molecular mechanism of iron dissociation from ENT in P. aeruginosa differs from that previously described in E. coli. In P. aeruginosa, siderophore hydrolysis occurs in the periplasm, with ENT never reaching the bacterial cytoplasm. In E. coli, ferri-ENT crosses the inner membrane via the ABC transporter FepBCD and ferri-ENT is hydrolyzed by the esterase Fes only once it is in the cytoplasm.

Published
2018

13. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells

Author

Emma Partiot, Nilda Vanesa Ayala-Nunez, Jacky G. Goetz, Gautier Follain, Judith R.E. Roels, Anita Eckly, Béatrice Uring-Lambert, Maxime Chazal, Raphael Gaudin, Gillian Hale, Frank M. J. Jacobs, Sandrine Bourdoulous, Orestis Faklaris, Sherif R. Zaki, Aurélie Hirschler, Nolwenn Jouvenet, Margot Carocci, Florian Bakoa, Sarah Cianférani, Christine Carapito, Frédéric Doussau, Brigid C. Bollweg, François Delalande, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Swammerdam Institute for Life Sciences, University of Amsterdam [Amsterdam] (UvA)-Center for Neurosciences, Génomique virale et vaccination, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5), 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), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion, Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), This work has received funding from the French State via the French National Research Agency (ANR) as part of the program Investissements d’avenir (IdEx Université de Strasbourg) to RG. This work was supported by an ATIP-AVENIR starting grant to RG. The research leading to these results has received funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program (FP7/2007–2013) under REA grant agreement no. PCOFUND-GA-2013-609102, through the PRESTIGE program coordinated by Campus France, and from the French Agency for Research on AIDS and Viral Hepatitis (ANRS), both attributed to NVAN. Experiments conducted by G.F. and J.G.G. were funded by Plan Cancer (OptoMetaTrap), Ligue contre le Cancer, Idex Attractivités (University of Strasbourg), and by institutional funds from INSERM and University of Strasbourg. G.F. was supported by a doctoral fellowship from Ligue Contre le Cancer. Mass spectrometry experiments were supported by the French Proteomic Infrastructure (ProFI, ANR-10-INBS-08-03). F.B. is a recipient of a PhD grant provided by ANRT (Association Nationale de la Recherche et de la Technologie). N.J. is funded by Agence Nationale pour la Recherche (ANR-16-CE15-0025-01), Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur. CDC contributions to this paper written and edited by G.L.H. and B.C.B. in their private capacity. No official support or endorsement by the Centers for Disease Control and Prevention, Department of Health and Human Services is intended, nor should be inferred. All authors read, provided feedback, and approved the paper. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 NL4-3 AD8 Infectious Molecular Clone (pNL(AD8)) from Dr. Eric O. Freed (cat# 11346)., ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l'infection virale(2016), European Project: 609102,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,PRESTIGE(2014), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), 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), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), EFS-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), jouvenet, nolwenn, Mécanismes de production incontrôlée de cytokines au cours de l'infection virale - - Viro-Storm2016 - ANR-16-CE15-0025 - AAPG2016 - VALID, PRES Towards International Gain of Excellence - PRESTIGE - - EC:FP7:PEOPLE2014-09-01 - 2019-08-31 - 609102 - VALID, Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Neuro-Immunologie Virale, Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de Photonique Quantique et Moléculaire (LPQM), Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-École normale supérieure - Cachan (ENS Cachan), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion (http://www.u949.inserm.fr/), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique, Département des Sciences Analytiques, Institut Pluridisciplinaire Hubert Curien, Strasbourg, France (LSMBO-DSA-IPHC), Centre National de la Recherche Scientifique (CNRS), Immunorhumathologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Molecular Neuroscience (SILS, FNWI)

Subjects
Central Nervous System, 0301 basic medicine, MESH: Neurons, General Physics and Astronomy, MESH: Organoids, MESH: Monocytes, Monocytes, Zika virus, 0302 clinical medicine, MESH: Transendothelial and Transepithelial Migration, Cerebellum, MESH: Animals, lcsh:Science, MESH: Embryonic Stem Cells, ComputingMilieux_MISCELLANEOUS, Zebrafish, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neurons, Multidisciplinary, Zika Virus Infection, Cell adhesion molecule, food and beverages, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Phenotype, 3. Good health, Cell biology, Organoids, Mechanisms of disease, medicine.anatomical_structure, MESH: Cell Survival, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Endothelium, Cell Survival, Science, MESH: Zika Virus, Biology, MESH: Endothelium, Article, General Biochemistry, Genetics and Molecular Biology, Virus, MESH: Cell Adhesion, 03 medical and health sciences, Virology, medicine, Animals, Humans, MESH: Central Nervous System, Cellular microbiology, Cell adhesion, MESH: Zebrafish, Embryonic Stem Cells, MESH: Humans, Monocyte, fungi, Transendothelial and Transepithelial Migration, Zika Virus, General Chemistry, biology.organism_classification, Embryonic stem cell, MESH: Cerebellum, Disease Models, Animal, 030104 developmental biology, lcsh:Q, MESH: Disease Models, Animal, Cell Adhesion Molecules, MESH: Female, 030217 neurology & neurosurgery
Abstract

Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention., Zika virus (ZIKV) can infect the central nervous system, but it is not clear how it reaches the brain. Here, Ayala-Nunez et al. show in ex vivo and in vivo models that ZIKV can hitch a ride in monocytes in a Trojan Horse manner to cross the endothelium and disseminate the virus.

Published
2019

14. Skin Interface, a Key Player for Borrelia Multiplication and Persistence in Lyme Borreliosis

Author

Nathalie Boulanger, Laurence Ehret-Sabatier, Cédric Lenormand, Antoine Grillon, Quentin Bernard, Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, 030231 tropical medicine, Aucun, Disease, Tick, 03 medical and health sciences, 0302 clinical medicine, vector-borne diseases, Borrelia, [CHIM]Chemical Sciences, Skin immunity, Animals, Humans, Borrelia burgdorferi, Pathogen, Skin, saliva, Lyme Disease, biology, Ixodes, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, bacterial infections and mycoses, biology.organism_classification, skin immunity, tick, 3. Good health, 030104 developmental biology, Infectious Diseases, Infectious disease (medical specialty), Immunology, Parasitology, immunotolerance
Abstract

International audience; The skin plays a key role in vector-borne diseases because it is the site where the arthropod coinoculates pathogens and its saliva. Lyme borreliosis, particularly well investigated in this context, is a multisystemic infectious disease caused by Borrelia burgdorferi sensu lato and transmitted by the hard tick Ixodes. Numerous in vitro studies were conducted to better understand the role of specific skin cells and tick saliva in host defense, vector feeding, and pathogen transmission. The skin was also evidenced in various animal models as the site of bacterial multiplication and persistence. We present the achievements in this field as well as the gaps that impede comprehensive knowledge of the disease pathophysiology and the development of efficient diagnostic tools and vaccines in humans. Copyright © 2020 Elsevier Ltd. All rights reserved.

Published
2019

15. Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies

Author

Gocko, X. (X), Lenormand, C. (C), Lemogne, C. (C), Bouiller, K. (K), Gehanno, J.-F., Rabaud, C. (C), Perrot, S. (S), Eldin, C. (C), de Broucker, T. (T), Roblot, F. (F), Toubiana, J. (J), Sellal, F. (Francois), Vuillemet, F. (F), Sordet, C. (Christelle), Fantin, B. (B), Lina, G. (G), Sobas, C. (C), Jaulhac, B. (Benoit), Figoni, J. (J), Chirouze, C. (C), Hansmann, Y. (Yves), Hentgen, V. (V), Caumes, E. (E), Dieudonné, M. (M), Picone, O. (O), Bodaghi, B. (B), Gangneux, J.-P., Degeilh, B. (B), Partouche, H. (H), Saunier, A. (A), Sotto, A. (A), Raffetin, A. (A), Monsuez, J.-J., Michel, C. (C), Boulanger, N. (Nathalie), Cathebras, P. (P), Tattevin, P. (P), societies, e. (endorsed) b. (by) t. (the) f. (following) s. (scientific), Université de Strasbourg (UNISTRA), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm - Paris Descartes), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de santé au travail et pathologie professionnelle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Max Weber (CMW), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet [Saint-Étienne] (UJM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Laboratoire Chrono-environnement (UMR 6249) (LCE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Societies, Scientific, Insecticides, [SDV]Life Sciences [q-bio], Aucun, MEDLINE, 03 medical and health sciences, 0302 clinical medicine, Environmental health, medicine, Animals, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Tick-borne disease, Lyme Disease, Vaccines, Lyme borreliosis, business.industry, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, medicine.disease, 3. Good health, Primary Prevention, Infectious Diseases, Tick-Borne Diseases, France, Nervous System Diseases, business, 030217 neurology & neurosurgery
Abstract

International audience

Published
2019

16. The complex of ferric-enterobactin with its transporter from Pseudomonas aeruginosa suggests a two-site model

Author

Lucile Moynié, Rory P. McCaughan, Matteo Ceccarelli, Gaëtan L. A. Mislin, Etienne Baco, Isabelle J. Schalk, James H. Naismith, Stefan Milenkovic, Giuliano Malloci, Véronique Gasser, Malcolm G. P. Page, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Universita degli Studi di Cagliari [Cagliari], Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), University of St Andrews [Scotland], Jacobs University [Bremen], CNR Istituto Officina dei Materiali (IOM), Consiglio Nazionale delle Ricerche [Roma] (CNR), The Wellcome Trust, University of St Andrews. Biomedical Sciences Research Complex, and University of St Andrews. School of Chemistry

Subjects
0301 basic medicine, Siderophore, General Physics and Astronomy, Siderophores, 02 engineering and technology, medicine.disease_cause, Crystallography, X-Ray, Biochemistry, chemistry.chemical_compound, polycyclic compounds, lcsh:Science, Bacterial structural biology, Iron Radioisotopes, Multidisciplinary, biology, Chemistry, Pseudomonas, QR Microbiology, 021001 nanoscience & nanotechnology, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Pseudomonas aeruginosa, 0210 nano-technology, Crystallization, Bacterial Outer Membrane Proteins, Science, Iron, Receptors, Cell Surface, In Vitro Techniques, General Biochemistry, Genetics and Molecular Biology, Article, Enterobactin, 03 medical and health sciences, Bacterial Proteins, medicine, Escherichia coli, Binding site, X-ray crystallography, Binding Sites, Membrane Proteins, DAS, Transporter, General Chemistry, Periplasmic space, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR, 030104 developmental biology, lcsh:Q, Carrier Proteins, Bacteria
Abstract

Bacteria use small molecules called siderophores to scavenge iron. Siderophore-Fe3+ complexes are recognised by outer-membrane transporters and imported into the periplasm in a process dependent on the inner-membrane protein TonB. The siderophore enterobactin is secreted by members of the family Enterobacteriaceae, but many other bacteria including Pseudomonas species can use it. Here, we show that the Pseudomonas transporter PfeA recognises enterobactin using extracellular loops distant from the pore. The relevance of this site is supported by in vivo and in vitro analyses. We suggest there is a second binding site deeper inside the structure and propose that correlated changes in hydrogen bonds link binding-induced structural re-arrangements to the structural adjustment of the periplasmic TonB-binding motif., Bacteria produce small iron-binding molecules called siderophores, which are recognised by outer-membrane transporters. Here, the authors show that a Pseudomonas transporter recognises the siderophore enterobactin using extracellular loops distant from the pore, and propose that there is a second binding site deeper inside the structure.

Published
2019

17. Impact of Setting up an 'Endocarditis Team' on the Management of Infective Endocarditis

Author

Nicolas Lefebvre, Yves Hansmann, Tam Hoang Minh, Xavier Argemi, François Lefebvre, N. Douiri, Philippe Riegel, Hélène Petit-Eisenmann, Yvon Ruch, Jean-Philippe Mazzucotelli, A. Martin, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), and Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë

Subjects
medicine.medical_specialty, Multivariate analysis, Aucun, 030204 cardiovascular system & hematology, valve disease, Major Articles, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Clinical endpoint, medicine, multidisciplinary management, Endocarditis, 030212 general & internal medicine, guidelines, Endocarditis Team, business.industry, infective endocarditis, Mortality rate, Odds ratio, medicine.disease, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Confidence interval, Cardiac surgery, Editor's Choice, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Oncology, Infective endocarditis, prognosis, business, cardiac surgery
Abstract

Background Infective endocarditis (IE) remains a severe disease with a high mortality rate. Therefore, guidelines encourage the setup of a multidisciplinary group in reference centers. The present study evaluated the impact of this “Endocarditis Team” (ET). Methods We conducted a monocentric observational study at Strasbourg University Hospital, Strasbourg, France, between 2012 and 2017. The primary end point was in-hospital mortality. Secondary end points were 6-month and 1-year mortality, surgery rate, time to surgical procedure, duration of effective antibiotic therapy, length of in-hospital stay, and sequelae. We also assessed predictors of in-hospital mortality. Results We analyzed 391 episodes of IE. In the post-ET period, there was a nonsignificant decrease in in-hospital mortality (20.3% vs 14.7%, respectively; P = .27) and sequelae, along with a significant reduction in time to surgery (16.4 vs 10.3 days, respectively; P = .049), duration of antibiotic therapy (55.2 vs 47.2 days, respectively; P < .001), and length of in-hospital stay (40.6 vs 31.9 days, respectively; P < .01). In a multivariate analysis, the post-ET period was positively associated with survival (odds ratio, 0.45; 95% confidence interval, 0.20–0.96; P = .048). Conclusions This multidisciplinary approach exerted a positive impact on the management of IE and should be considered in all hospitals managing IE., The implementation of an 'Endocarditis Team' is recommended in reference centres for infective endocarditis. This study evaluated its impact and showed improvements on the management of this disease with a decrease in time to surgery and nonsignificant reduction in mortality.

Published
2019

18. Characteristics and clinical outcomes after treatment of a national cohort of PCR-positive Lyme arthritis

Author

Marc Scherlinger, Didier Eyer, Aleth Perdriger, Amandine Blasquez, Frédéric Bastides, Laurence Zilliox, François Guérin, Jean-Marie Woehl, Antoine Grillon, Yves Maugars, Pierre-Hugues Boyer, Alain Cantagrel, Antoine Colombey, Paul Moreau, Jean Sibilia, François Cuchet, Anne-Sophie Korganow, Christian Bonnard, Julien Wipff, Joel Lechevallier, Isabelle Imbert, Irène Monteiro, Jean-Loup Pennaforte, Laurent Arnaud, Philippe Gicquel, Michel Brax, Benoît Jaulhac, Sylvie De Martino, Cathy Barthel, Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Immuno-Rhumatologie Moléculaire, and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Arthritis, Lyme Arthritis, Polymerase Chain Reaction, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Rheumatology, Internal medicine, Borrelia, Synovitis, Synovial Fluid, Medicine, Synovial fluid, Humans, 030212 general & internal medicine, Child, Aged, 030203 arthritis & rheumatology, Doxycycline, Lyme Disease, biology, business.industry, Amoxicillin, Middle Aged, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, 3. Good health, Anti-Bacterial Agents, Anesthesiology and Pain Medicine, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Polyarthritis, Female, France, business, medicine.drug
Abstract

To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Objectives To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Methods Using the French National Reference Center for Borrelia database, patients with a positive PCR on synovial fluid for Borrelia were identified. Patient clinical and biological characteristics were reviewed from patient records. Long-term outcomes after treatment were studied through a questionnaire and with follow-up data. Results Among 357 synovial fluid testing by PCR between 2010 and 2016, 37 (10.4%) were positive for Borrelia. Patients’ median age was 36 years (range 6–78) with 61% of men and 28% patients under 18. The presentation was monoarticular in 92% and the knee was involved in 97%. Contrary to the Borrelia species repartition in European ticks, B. burgdorferi sensu stricto was the most prevalent species found in synovial fluid (54%) followed by B. azfelii (29%) and B. garinii (17%). Antibiotic treatments were mainly composed of doxycycline (n = 24), ceftriaxone (n = 10) and amoxicillin (n = 6), for a median duration of 4 weeks (range 3–12). Despite a properly conducted treatment, 34% of patients (n = 12) developed persistent synovitis for at least 2 months (median duration 3 months, range 2–16). Among those, 3 developed systemic inflammatory oligo- or polyarthritis in previously unaffected joints with no signs of persistent infection (repeated PCR testing negative), which mandated Disease-Modifying Antirheumatic Drugs (DMARD) introduction, leading to remission. Conclusion In France and contrary to ticks ecology, Lyme arthritis is mainly caused by B. burgdorferi sensu stricto. Despite proper antibiotic therapy, roughly one third of patients may present persistent inflammatory synovitis and a small proportion may develop systemic arthritis. In such cases, complete remission can be reached using DMARD. journal article 2019 06 2018 09 28 imported

Published
2019

19. Portraying infective endocarditis

Author

Ilker Inanc Balkan, Najada Como, André Silva-Pinto, Antonio Cascio, Canan Agalar, Meliha Meric-Koc, Tatjana Lejko Zupanc, Oday Abu Ajamieh, Simin Aysel Florescu, Selma Tosun, Meltem Taşbakan, Asuman Inan, Rosa Fontana Del Vecchio, Edmond Puca, Güven Çelebi, Ayse Sagmak-Tartar, Abdullah Umut Pekok, Yasemin Cag, Gülden Ersöz, Sumeyra Karakus, Safak Ozer-Balin, Jamal Wadi, Sukran Kose, Yves Hansmann, Hacer Deniz Ozkaya, Nefise Oztoprak, Hakan Erdem, Serkan Oncu, Jesper Damsgaard Gunst, Yvon Ruch, Aysegul Erdem, Gilda Tonziello, Ayse Batirel, Rahmet Guner, Irina Magdalena Dumitru, Lurdes Santos, Raquel Duro, Nesrin Ghanem-Zoubi, Arjeta Dedej, Serda Gulsun, Mustafa Dogan, Necla Tulek, Alper Şener, Pedro Palma Martins, Ilkay Bozkurt, Deborah Konopnicki, Fatma Sirmatel, Xavier Argemi, Meltem Avci, Fahad Almajid, Recep Tekin, Nicola Petrosillo, Corneliu Petru Popescu, Ayse Kaya-Kalem, Imran Hasanoglu, Atilla Iyisoy, Jean Philippe Mazzucotelli, Ejaz Ahmed Khan, Sema Sarı, Derya Ozturk-Engin, Nicolas Dauby, Erdem H., Puca E., Ruch Y., Santos L., Ghanem-Zoubi N., Argemi X., Hansmann Y., Guner R., Tonziello G., Mazzucotelli J.-P., Como N., Kose S., Batirel A., Inan A., Tulek N., Pekok A.U., Khan E.A., Iyisoy A., Meric-Koc M., Kaya-Kalem A., Martins P.P., Hasanoglu I., Silva-Pinto A., Oztoprak N., Duro R., Almajid F., Dogan M., Dauby N., Gunst J.D., Tekin R., Konopnicki D., Petrosillo N., Bozkurt I., Wadi J., Popescu C., Balkan I.I., Ozer-Balin S., Zupanc T.L., Cascio A., Dumitru I.M., Erdem A., Ersoz G., Tasbakan M., Ajamieh O.A., Sirmatel F., Florescu S., Gulsun S., Ozkaya H.D., Sari S., Tosun S., Avci M., Cag Y., Celebi G., Sagmak-Tartar A., Karakus S., Sener A., Dedej A., Oncu S., Del Vecchio R.F., Ozturk-Engin D., Agalar C., Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), MERİÇ KOÇ, MELİHA, İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Uşak Üniversitesi, Zonguldak Bülent Ecevit Üniversitesi, BAİBÜ, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Sırmatel, Fatma, and OMÜ

Subjects
Male, Internationality, Aucun, Infective endocarditi, medicine.disease_cause, Medical microbiology, 80 and over, Blood culture, Hospital Mortality, Aged, 80 and over, medicine.diagnostic_test, biology, Endocarditis, Bacterial, General Medicine, Sciences bio-médicales et agricoles, Middle Aged, Staphylococcal Infections, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Viridans Streptococci, Catheter, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Staphylococcus aureus, Infective endocarditis, Aortic Valve, Mitral Valve, Female, Microbiology (medical), Adult, medicine.medical_specialty, Prosthesis-Related Infections, Adolescent, aureus, Young Adult, Internal medicine, medicine, Humans, results of multinational ID-IRI study-, EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES, cilt.38, ss.1753-1763, 2019 [Erdem H., Puca E., Ruch Y., Santos L., Ghanem-Zoubi N., Argemi X., Hansmann Y., Guner R., Tonziello G., Mazzucotelli J., et al., -Portraying infective endocarditis], Prosthetic, Aged, Native Valve Endocarditis, Bacteria, business.industry, Endocarditis, Bacterial, medicine.disease, biology.organism_classification, S. aureus, Viridans streptococci, business, Native
Abstract

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042)., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

20. Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis: prevention, epidemiology, diagnosis

Author

Figoni, J. (J), Chirouze, C. (C), Hansmann, Y. (Yves), Lemogne, C. (C), Hentgen, V. (V), Saunier, A. (A), Bouiller, K. (K), Gehanno, J. (J) F. (F), Rabaud, C. (C), Perrot, S. (S), Caumes, E. (E), Eldin, C. (C), de Broucker, T. (T), Jaulhac, B. (Benoit), Roblot, F. (F), Toubiana, J. (J), Sellal, F. (Francois), Vuillemet, F. (F), Sordet, C. (Christelle), Fantin, B. (B), Lina, G. (G), Gocko, X. (X), Dieudonné, M. (M), Picone, O. (O), Bodaghi, B. (B), Gangneux, J. (J) P. (P), Degeilh, B. (B), Partouche, H. (H), Lenormand, C. (Cedric), Sotto, A. (A), Raffetin, A. (A), Monsuez, J. (J) J. (J), Michel, C. (C), Boulanger, N. (Nathalie), Cathebras, P. (P), and Tattevin, P. (P)

Subjects
Aucun, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Abstract

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50–100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (< 10 cases/year), and babesiosis (< 5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (< 15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

Published
2019

21. Dissociating effect of salivary gland extract from Ixodes ricinus on human fibroblasts: Potential impact on Borrelia transmission

Author

Boeuf, A. (Amandine), Schnell, G. (Gilles), Bernard, Q. (Quentin), Kern, A. (Aurelie), Westermann, B. (Benoît), Sabatier, L. (Laurence), Grillon, A. (Antoine), Schramm, F. (Frederic), Jaulhac, B. (Benoit), and Boulanger, N. (Nathalie)

Subjects
Aucun, bacterial infections and mycoses, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Abstract

Understanding the mechanism of pathogen transmission is essential for the development of strategies to reduce arthropod-borne diseases. The pharmaco- and immunomodulatory properties of insect and acarine saliva play an essential role in the efficiency of pathogen transmission. The skin as the site where arthropod saliva and pathogens are inoculated - represents the key interface in vector-borne diseases. We identified tick molecules potentially involved in pathogen transmission, using micro-HPLC and mass spectrometry, followed by in vitro assays on human skin cells. Histone H4 isolated from Ixodes ricinus salivary gland extract was identified as a molecule with a dissociating effect on human primary fibroblasts. This histone might be involved in the formation of the feeding pool formed around the tick mouthparts and responsible of tissue necrosis in the vertebrate host. Thanks to its selective antimicrobial activity, it may also sterilize the feeding pool and facilitate transmission of pathogens such as Borrelia burgdorferi sensu lato.

Published
2019

22. Non-specific interference of cobalt with siderophore-dependent iron uptake pathways

Author

Bénédicte Pesset, Pamela Saint Auguste, Olivier Cunrath, Dirk Bumann, Odile Sismeiro, Julien Pérard, Quentin Perraud, Isabelle Michaud-Soret, Isabelle J. Schalk, Rachel Legendre, Anne Forster, Pierre Fechter, Ana Carballido Lopez, Jean Yves Coppée, Gaëtan L. A. Mislin, Gwenaëlle Graulier, Hugo Varet, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Focal Area Infection Biology, Biozentrum, University of Basel (Unibas), This work was partly funded by the Centre National de la Recherche Scientifique. O. Cunrath held a fellowship from the French Ministère de la Recherche et de la Technologie (3 years) and the FRM (Fondation pour la Recherche Médicale, 6 months). A. Y. Carballido Lopez held a fellowship from the University of Strasbourg (IDEX) and B. Pesset from the DGA (Direction Générale des l’Armement). J. P. and I. M. S. thank the Laboratory of Excellence GRAL (grant ANR-11-LABX-49-01) and the Labex ARCANE (grant ANR-11-LABX-0003-01). The Transcriptome and Epigenome Platform is a member of the France Génomique consortium (ANR10-NBS-09-08)., We thank Dr A. Boos and P. Ronot (Institut Pluridisciplinaire Hubert Curien, Strasbourg) for their help in the ICP-AES measurements., ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), Biologie des Métaux (BioMet), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Bioinformatique évolutive - Evolutionary Bioinformatics, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, inorganic chemicals, Siderophore, Iron, Biophysics, Down-Regulation, Siderophores, Biochemistry, Models, Biological, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, Biosynthesis, Bacterial Proteins, Phenols, Operon, medicine, Transcriptional regulation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Psychological repression, 030102 biochemistry & molecular biology, biology, Chemistry, Metals and Alloys, Transporter, Cobalt, Gene Expression Regulation, Bacterial, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Up-Regulation, Thiazoles, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Chemistry (miscellaneous), Pseudomonas aeruginosa, Ferric, Bacterial outer membrane, Oligopeptides, Bacteria, medicine.drug
Abstract

International audience; Much data shows that biological metals other than Fe3+ can interfere with Fe3+ acquisition by siderophores in bacteria. Siderophores are small Fe3+ chelators produced by the microorganisms to obtain access to Fe3+. Here, we show that Co2+ is imported into Pseudomonas aeruginosa cells in a complex with the siderophore pyochelin (PCH) by the ferri-PCH outer membrane transporter FptA. Moreover, the presence of Co2+ in the bacterial environment strongly affects the production of PCH. Proteomic and transcriptomic approaches showed that a decrease of PCH production is associated with repression of the expression of the genes involved in PCH biosynthesis. We used various molecular biology approaches to show that this repression is not Fur-(ferric uptake transcriptional regulator) dependent but due to competition of PCH-Co with PCH-Fe for PchR (transcriptional activator), thus inhibiting the formation of PchR-PCH-Fe and consequently the expression of the PCH genes. We observed a similar mechanism of repression of PCH production, but to a lesser extent, by Ni2+, but not for Zn2+, Cu2+, or Mn2+. Here, we show, for the first time at a molecular level, how the presence of a contaminant metal can interfere with Fe3+ acquisition by the siderophores PCH and PVD.

Published
2019

23. Interaction of a Model Peptide on Gram Negative and Gram Positive Bacterial Sliding Clamps

Author

Vincent Olieric, Bernard Lorber, Jérôme Wagner, Dominique Burnouf, Annick Dejaegere, Gilles Guichard, Philippe Dumas, Marie Landolfo, C. Andre, Isabelle Martiel, Cyrielle Da Veiga, Philippe Wolff, Univ Bordeaux, CNRS UMR 5248, Inst Chim & Biol Membranes & Nanoobjets, INP Bordeaux, Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), GUICHARD, Gilles, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), The Swiss Light Source (SLS) (SLS-PSI), Paul Scherrer Institute (PSI), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
Models, Molecular, DNA polymerase, Protein Conformation, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Peptide, DNA-Directed DNA Polymerase, 010402 general chemistry, Crystallography, X-Ray, Gram-Positive Bacteria, Ligands, Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire, 01 natural sciences, Microbiology, 03 medical and health sciences, Drug Development, Escherichia coli, kinITC, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Antibacterial drug, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Gram, Nucleic Acid Synthesis Inhibitors, sliding clamp, chemistry.chemical_classification, new antibacterials development, 0303 health sciences, [CHIM.MATE] Chemical Sciences/Material chemistry, DNA clamp, biology, [CHIM.MATE]Chemical Sciences/Material chemistry, ITC, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 0104 chemical sciences, Anti-Bacterial Agents, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Infectious Diseases, chemistry, Mutation, biology.protein, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Peptides, ligand−target interaction, Protein Binding
Abstract

Bacterial sliding clamps control the access of DNA polymerases to the replication fork and are appealing targets for antibacterial drugs development. It is therefore essential to decipher the polymerase-clamp binding mode across various bacterial species. Here, two residues of the E. coli clamp binding pocket, EcS346 and EcM362, and their cognate residues in M. tuberculosis and B. subtilis clamps, were mutated. The effects of these mutations on the interaction of a model peptide with these variant clamps were evaluated by thermodynamic, molecular dynamics, X-rays crystallography and biochemical analyses. EcM362 and corresponding residues in Gram positive clamps occupy a strategic position where a mobile residue is essential for an efficient peptide interaction. EcS346 has a more subtle function that modulates the pocket folding dynamics, while the equivalent residue in B. subtilis is essential for polymerase activity and might therefore be a Gram positive specific molecular marker. Finally, the peptide binds through an induced-fit process to Gram negative and positive pockets but the complex stability varies according to a pocket specific network of interactions. The following values have no corresponding Zotero field:auth-address: 1 Institut Européen de Chimie et Biologie , Université de Bordeaux-CNRS UMR 5248, CBMN , 2, rue Robert Escarpit , 33607 Pessac , France. 2 Swiss Light Source (SLS) , Paul-Scherrer-Institute (PSI) , 5232 Villigen , Switzerland. 3 Université de Strasbourg , CNRS, Architecture et Réactivité de l'ARN, UPR 9002, Institut de Biologie Moléculaire et Cellulaire du CNRS , 15 rue René Descartes , F-67000 Strasbourg , France. 4 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) , Département de Biologie Structurale et Génomique , 1 rue Laurent Fries , BP10142, 67404 Illkirch , France. 5 Biologie et Signalisation Cellulaire, ESBS , UMR7242 CNRS/Université de Strasbourg , Bld S. Brant , 67412 Illkirch Cedex , France.accession-num: 30912430

Published
2019

24. Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis

Author

C Sordet, Carole Eldin, Figoni J, Cathebras P, Pierre Tattevin, Yves Hansmann, Brigitte Degeilh, Sobas C, Maël Dieudonné, Julie Toubiana, Perrot S, Eric Caumes, Benoît Jaulhac, V Hentgen, N Boulanger, Jean-Jacques Monsuez, F. Roblot, Jean-François Gehanno, B Bodaghi, Cédric Lemogne, Gocko X, A Saunier, F Vuillemet, Olivier Picone, Christian Rabaud, T. de Broucker, Albert Sotto, endorsed by scientific societies, Catherine Chirouze, Cédric Lenormand, Catherine Michel, François Sellal, Gerard Lina, Kevin Bouiller, Bruno Fantin, A. Raffetin, Jean-Pierre Gangneux, Henri Partouche, CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de santé au travail et pathologie professionnelle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Hautepierre [Strasbourg], Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Max Weber (CMW), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm - Paris Descartes), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pitié-Salpêtrière [APHP], Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet [Saint-Étienne] (UJM)

Subjects
Societies, Scientific, medicine.medical_specialty, Erythema migrans, [SDV]Life Sciences [q-bio], Aucun, Western blot, Serology, Diagnosis, Differential, Borréliose de Lyme, 03 medical and health sciences, medicine, Érythème migrant, Animals, Humans, Seroconversion, ComputingMilieux_MISCELLANEOUS, Lyme borreliosis, Symptomatologie somatique persistante, Doxycycline, Lyme Disease, 0303 health sciences, Tick-borne disease, Clinical Laboratory Techniques, 030306 microbiology, business.industry, Neuroborreliosis, Amoxicillin, medicine.disease, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Dermatology, Persistent somatic symptoms, 3. Good health, LYME, Infectious Diseases, Tick-Borne Diseases, Practice Guidelines as Topic, Disease Progression, France, business, Neuroborréliose, medicine.drug
Abstract

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them. endorsed by scientific societies

Published
2019

25. Genetic and transcriptomic analyses provide new insights on the early antiviral response to VHSV in resistant and susceptible rainbow trout

Author

Verrier, Eloi R., Genet, Carine, Laloë, Denis, Jaffrezic, Florence, Rau, Andrea, Esquerre, Diane, Dechamp, Nicolas, Ciobotaru, Céline, Hervet, Caroline, Krieg, Francine, Jouneau, Luc, Klopp, Christophe, Quillet, Edwige, Boudinot, Pierre, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), Unité de Biométrie et Intelligence Artificielle de Toulouse [Castanet-Tolosan] (UBIA), Institut National de la Recherche Agronomique (INRA)-Plateforme bioinformatique du GIS GENOTOUL - Génopole Toulouse Midi-Pyrénées, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), AgroParisTech-Institut National de la Recherche Agronomique (INRA), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, INRA Action incitative 'Bioressources' AntiVIC-RS 2010, European Project: 228394,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2008-1,NADIR(2009), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Unité de Biométrie et Intelligence Artificielle (ancêtre de MIAT) (UBIA)

Subjects
lcsh:QH426-470, VHSV, QTL, Gene Expression Profiling, lcsh:Biotechnology, animal diseases, Quantitative Trait Loci, rainbow trout, antiviral resistance, Transcriptome deep sequencing, qtl, High-Throughput Nucleotide Sequencing, Antiviral resistance, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Immunity, Innate, Cell Line, Fish Diseases, lcsh:Genetics, Rainbow trout, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oncorhynchus mykiss, lcsh:TP248.13-248.65, Animals, Disease Susceptibility, Interferons, Research Article
Abstract

Background The viral hemorrhagic septicemia virus (VHSV) is a major threat for salmonid farming and for wild fish populations worldwide. Previous studies have highlighted the importance of innate factors regulated by a major quantitative trait locus (QTL) for the natural resistance to waterborne VHSV infection in rainbow trout. The aim of this study was to analyze the early transcriptomic response to VHSV inoculation in cell lines derived from previously described resistant and susceptible homozygous isogenic lines of rainbow trout to obtain insights into the molecular mechanisms responsible for the resistance to the viral infection. Results We first confirmed the presence of the major QTL in a backcross involving a highly resistant fish isogenic line (B57) and a highly susceptible one (A22), and were able to define the confidence interval of the QTL and to identify its precise position. We extended the definition of the QTL since it controls not only resistance to waterborne infection but also the kinetics of mortality after intra-peritoneal injection. Deep sequencing of the transcriptome of B57 and A22 derived cell lines exposed to inactivated VHSV showed a stronger response to virus inoculation in the resistant background. In line with our previous observations, an early and strong induction of interferon and interferon-stimulated genes was correlated with the resistance to VHSV, highlighting the major role of innate immune factors in natural trout resistance to the virus. Interestingly, major factors of the antiviral innate immunity were much more expressed in naive B57 cells compared to naive A22 cells, which likely contributes to the ability of B57 to mount a fast antiviral response after viral infection. These observations were further extended by the identification of several innate immune-related genes localized close to the QTL area on the rainbow trout genome. Conclusions Taken together, our results improve our knowledge in virus-host interactions in vertebrates and provide novel insights in the molecular mechanisms explaining the resistance to VHSV in rainbow trout. Our data also provide a collection of potential markers for resistance and susceptibility of rainbow trout to VHSV infection. Electronic supplementary material The online version of this article (10.1186/s12864-018-4860-1) contains supplementary material, which is available to authorized users.

Published
2018

26. Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection

Author

Mathilde Munier, Isabelle J. Schalk, Françoise Hoegy, Véronique Gasser, Nicolas Zill, Paola Cantero, Quentin Perraud, Laurence Ehret-Sabatier, Gaëtan L. A. Mislin, Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), Siderophore, siderophore, TonB dependent transporters, medicine.drug_class, Antibiotics, Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire, medicine.disease_cause, Microbiology, Article, antibiotics, 03 medical and health sciences, siderophore–antibiotic, Virology, Sense (molecular biology), vectorization, medicine, hal-03085895, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, proteomic, 030102 biochemistry & molecular biology, biology, Chemistry, Pseudomonas aeruginosa, iron uptake, Transporter, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Phenotype, Epithelium, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), Bacteria
Abstract

Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake process. P. aeruginosa produces two siderophores and is also able to use many siderophores produced by other bacteria. We investigated the phenotypic plasticity of iron-uptake pathway expression in an epithelial cell infection assay in the presence of two different siderophore&ndash, antibiotic conjugates, one with a hydroxamate siderophore and the second with a tris-catechol. Proteomic and RT-qPCR approaches showed that P. aeruginosa was able to sense the presence of both compounds in its environment and adapt the expression of its iron uptake pathways to access iron via them. Moreover, the catechol-type siderophore&ndash, antibiotic was clearly more efficient in inducing the expression of its corresponding transporter than the hydroxamate compound when both were simultaneously present. In parallel, the expression of the proteins of the two iron uptake pathways using siderophores produced by P. aeruginosa was significantly repressed in the presence of both conjugates. Altogether, the data indicate that catechol-type siderophores are more promising vectors for antibiotic vectorization using a Trojan-horse strategy.

Published
2020

27. Siderophore–antibiotic conjugates: exploiting iron uptake to deliver drugs into bacteria

Author

Schalk, Isabelle, Schalk, I.J., Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), Siderophore, medicine.drug_class, Iron, 030106 microbiology, Antibiotics, Siderophores, Microbial Sensitivity Tests, Drug resistance, Microbiology, 03 medical and health sciences, Drug Resistance, Bacterial, Gram-Negative Bacteria, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Iron uptake, Bacteria, biology, Chemistry, General Medicine, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Anti-Bacterial Agents, 030104 developmental biology, Infectious Diseases, Conjugate
Abstract

International audience

Published
2018

28. Multilocus sequence typing of clinical Borreliella afzelii strains: population structure and differential ability to disseminate in humans

Author

Gallais, F. (Floriane), De Martino, S. (Sylvie) J. (J), Sauleau, E. (Eric-André) A. (A), Hansmann, Y. (Yves), Lipsker, D. (Dan), Lenormand, C. (Cédric), Talagrand-Reboul, E. (Emilie), Boyer, P. (Pierre) H. (H), Boulanger, N. (Nathalie), Jaulhac, B. (Benoit), and Schramm, F. (Frederic)

Subjects
bacterial infections and mycoses, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Sciences du Vivant [q-bio]/Génétique
Abstract

BACKGROUND: Lyme borreliosis in humans results in a range of clinical manifestations, thought to be partly due to differences in the pathogenicity of the infecting strain. This study compared European human clinical strains of Borreliella afzelii (previously named Borrelia afzelii) using multilocus sequence typing (MLST) to determine their spatial distribution across Europe and to establish whether there are associations between B. afzelii genotypes and specific clinical manifestations of Lyme borreliosis. For this purpose, typing was performed on 63 strains, and data on a further 245 strains were accessed from the literature. RESULTS: All 308 strains were categorized into 149 sequence types (STs), 27 of which are described here for the first time. Phylogenetic and goeBURST analyses showed short evolutionary distances between strains. Although the main STs differed among the countries with the largest number of strains of interest (Germany, the Netherlands, France and Slovenia), the B. afzelii clinical strains were less genetically structured than those previously observed in the European tick population. Two STs were found significantly more frequently in strains associated with clinical manifestations involving erythema migrans, whereas another ST was found significantly more frequently in strains associated with disseminated manifestations, especially neuroborreliosis. CONCLUSIONS: The MLST profiles showed low genetic differentiation between B. afzelii strains isolated from patients with Lyme borreliosis in Europe. Also, clinical data analysis suggests the existence of lineages with differential dissemination properties in humans.

Published
2018

29. D-Cateslytin, a new antimicrobial peptide with therapeutic potential

Author

Abdurraouf Zaet, Pauline Dartevelle, Fadoua Daouad, Claire Ehlinger, Fabienne Quilès, Grégory Francius, Christian Boehler, Camille Bergthold, Benoît Frisch, Gilles Prévost, Philippe Lavalle, Francis Schneider, Youssef Haïkel, Marie-Hélène Metz-Boutigue, Céline Marban, Univ Strasbourg, INSERM, UMR S 1121, F-67085 Strasbourg, France, Faculté de chirurgie dentaire - Strasbourg, Université de Strasbourg (UNISTRA), Laboratoire de Chimie Physique et Microbiologie pour l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), FRANCIUS, GREGORY, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cell Survival, [SDV]Life Sciences [q-bio], Aucun, lcsh:Medicine, Firmicutes, Microbial Sensitivity Tests, Prevotella intermedia, Permeability, Article, Anti-Infective Agents, Cell Wall, [CHIM] Chemical Sciences, Escherichia coli, Humans, [CHIM]Chemical Sciences, lcsh:Science, Microbial Viability, lcsh:R, Cell Membrane, Drug Synergism, Epithelial Cells, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Peptide Fragments, Chromogranin A, lcsh:Q, Caco-2 Cells, Antimicrobial Cationic Peptides
Abstract

International audience; The rise of antimicrobial resistant microorganisms constitutes an increasingly serious threat to global public health. As a consequence, the efficacy of conventional antimicrobials is rapidly declining, threatening the ability of healthcare professionals to cure common infections. Over the last two decades host defense peptides have been identified as an attractive source of new antimicrobials. In the present study, we characterized the antibacterial and mechanistic properties of D-Cateslytin (D-Ctl), a new epipeptide derived from L-Cateslytin, where all L-amino acids were replaced by D-amino acids. We demonstrated that D-Ctl emerges as a potent, safe and robust peptide antimicrobial with undetectable susceptibility to resistance. Using Escherichia coli as a model, we reveal that D-Ctl targets the bacterial cell wall leading to the permeabilization of the membrane and the death of the bacteria. Overall, D-Ctl offers many assets that make it an attractive candidate for the biopharmaceutical development of new antimicrobials either as a single therapy or as a combination therapy as D-Ctl also has the remarkable property to potentiate several antimicrobials of reference such as cefotaxime, amoxicillin and methicillin.

Published
2017

31. Whole-Genome Sequencing of Seven Strains of Staphylococcus lugdunensis Allows Identification of Mobile Genetic Elements

Author

Argemi, Xavier, Martin, Véronique, Loux, Valentin, Dahyot, Sandrine, Lebeurre, Jérémie, Guffroy, Aurélien, Martin, Mickael, Velay, Aurélie, Keller, Daniel, Riegel, Philippe, Hansmann, Yves, Paul, Nicodème, and Prévost, Gilles

Subjects
next generation sequencing, Recombination, Genetic, plasmids, Genomic Islands, Virulence Factors, Prophages, Staphylococcus lugdunensis, Aucun, Molecular Sequence Annotation, Staphylococcal Infections, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Genome Report, virulence, Interspersed Repetitive Sequences, Genome, Bacterial
Abstract

Coagulase negative staphylococci are normal inhabitant of the human skin flora that account for an increasing number of infections, particularly hospital-acquired infections. Staphylococcus lugdunensis has emerged as a most virulent species causing various infections with clinical characteristics close to what clinicians usually observe with Staphylococcus aureus and both bacteria share more than 70% of their genome. Virulence of S. aureus relies on a large repertoire of virulence factors, many of which are encoded on mobile genetic elements. S. lugdunensis also bears various putative virulence genes but only one complete genome with extensive analysis has been published with one prophage sequence (φSL2) and a unique plasmid was previously described. In this study, we performed de novo sequencing, whole genome assembly and annotation of seven strains of S. lugdunensis from VISLISI clinical trial. We searched for the presence of virulence genes and mobile genetics elements using bioinformatics tools. We identified four new prophages, named φSL2 to φSL4, belonging to the Siphoviridae class and five plasmids, named pVISLISI_1 to pVISLISI_5. Three plasmids are homologous to known plasmids that include, amongst others, one S. aureus plasmid. The two other plasmids were not described previously. This study provides a new context for the study of S. lugdunensis virulence suggesting the occurrence of several genetic recombination' with other staphylococci.

Published
2017

32. Iron Uptake Analysis in a Set of Clinical Isolates of Pseudomonas putida

Author

Valérie Geoffroy, Zulema Udaondo, Ana Segura, Juan-Luis Ramos, Lázaro Molina, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Ministerio de Economía y Competitividad (España), and European Commission

Subjects
0301 basic medicine, Microbiology (medical), Siderophore, 030106 microbiology, Locus (genetics), Biology, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, iron, clinical strains, Clade, Gene, Ecological niche, Pyoverdine, pyoverdine, Pseudomonas putida, siderophores, Edaphic, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, biology.organism_classification, 3. Good health, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, bacteria
Abstract

Pseudomonas putida strains are frequent inhabitants of soil and aquatic niches and they are occasionally isolated from hospital environments. As the available iron sources in human tissues, edaphic, and aquatic niches are different, we have analyzed iron-uptake related genes in different P. putida strains that were isolated from all these environments. We found that these isolates can be grouped into different clades according to the genetics of siderophore biosynthesis and recycling. The pyoverdine locus of the six P. putida clinical isolates that have so far been completely sequenced, are not closely related; three strains (P. putida HB13667, HB3267, and NBRC14164T) are grouped in Clade I and the other three in Clade II, suggesting possible different origins and evolution. In one clinical strain, P. putida HB4184, the production of siderophores is induced under high osmolarity conditions. The pyoverdine locus in this strain is closely related to that of strain P. putida HB001 which was isolated from sandy shore soil of the Yellow Sea in Korean marine sand, suggesting their possible origin, and evolution. The acquisition of two unique TonB-dependent transporters for xenosiderophore acquisition, similar to those existing in the opportunistic pathogen P. aeruginosa PAO, is an interesting adaptation trait of the clinical strain P. putida H8234 that may confer adaptive advantages under low iron availability conditions., Work in our laboratories was supported by ERANET Pathogenomics program through the ADHERS project (Ref: BIO2008-04419-E) and Fondos FEDER from the European Union through project BIO2010-17227 of the Spanish Ministry of Economy and Competitivity. The work in Abengoa Research was funded by H2020 grant Empowerputida number 65703.

Published
2016

33. VISLISI trial, a prospective clinical study allowing identification of a new metalloprotease and putative virulence factor from Staphylococcus lugdunensis

Author

Philippe Riegel, C. Ronde Oustau, Yves Hansmann, Xavier Argemi, N. Douiri, M. Baldeyrou, Nicolas Meyer, Jean-Marc Strub, Daniel Christmann, Sarah Cianférani, Daniel Keller, K. Meghit, Gilles Prévost, Nicolas Lefebvre, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de bactériologie, Fédération de Médecine Translationelle de Strasbourg (FMTS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Phosphonoacetic Acid, medicine.medical_treatment, Aucun, medicine.disease_cause, Virulence factor, Methicillin, Drug Resistance, Multiple, Bacterial, Prospective Studies, Staphylococcus hyicus, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, biology, Staphylococcus lugdunensis, General Medicine, Middle Aged, Staphylococcal Infections, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Clumping factor A, 3. Good health, Erythromycin, Infectious Diseases, Staphylococcus aureus, Female, Fluoroquinolones, Microbiology (medical), Adult, DNA, Bacterial, Virulence Factors, 030106 microbiology, Virulence, Microbiology, 03 medical and health sciences, Fosfomycin, Vancomycin, medicine, [CHIM]Chemical Sciences, Humans, Amino Acid Sequence, Aged, Protease, Base Sequence, Sequence Analysis, DNA, biology.organism_classification, 030104 developmental biology, Aminoglycosides, Metalloproteases, Staphylococcus, Fusidic Acid, Follow-Up Studies
Abstract

Objective Staphylococcus lugdunensis is a coagulase-negative staphylococcus that displays an unusually high virulence rate close to that of Staphylococcus aureus . It also shares phenotypic properties with S. aureus and several studies found putative virulence factors. The objective of the study was to describe the clinical manifestations of S. lugdunensis infections and investigate putative virulence factors. Method We conducted a prospective study from November 2013 to March 2016 at the University Hospital of Strasbourg. Putative virulence factors were investigated by clumping factor detection, screening for proteolytic activity, and sequence analysis using tandem nano-liquid chromatography-mass spectrometry. Results In total, 347 positive samples for S. lugdunensis were collected, of which 129 (37.2%) were from confirmed cases of S. lugdunensis infection. Eighty-one of these 129 patients were included in the study. Bone and prosthetic joints (PJI) were the most frequent sites of infection ( n =28; 34.6%) followed by skin and soft tissues ( n =23; 28.4%). We identified and purified a novel protease secreted by 50 samples (61.7%), most frequently associated with samples from deep infections and PJI ( pr 0.97 and pr 0.91, respectively). Protease peptide sequencing by nano-liquid chromatography-mass spectrometry revealed a novel protease bearing 62.42% identity with ShpI, a metalloprotease secreted by Staphylococcus hyicus . Conclusion This study confirms the pathogenicity of S. lugdunensis , particularly in bone and PJI. We also identified a novel metalloprotease called lugdulysin that may contribute to virulence.

Published
2016

34. Catechol siderophores repress the pyochelin pathway and activate the enterobactin pathway in Pseudomonas aeruginosa : an opportunity for siderophore-antibiotic 2 conjugates development: Ability of to acquire iron via catechols

Author

Gasser, V. (Veronique), Baco, E. (Etienne), Cunrath, O. (Olivier), August, P. (Pamela Saint), Perraud, Q. (Quentin), Zill, N. (Nicolas), Schleberger, C. (Christian), Schmidt, A. (Alexander), Paulen, A. (Aurélie), Bumann, D. (Dirk), Mislin, G. (Gaetan), and Schalk, I. (Isabelle)

Subjects
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Published
2016

35. Rôles des sidérophores bactériens et de mammifères dans les interactions hôtes-pathogènes

Author

Sophie Vaulont, Isabelle J. Schalk, Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
Siderophore, biology, Phospholipid, General Medicine, medicine.disease_cause, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Small molecule, General Biochemistry, Genetics and Molecular Biology, Microbiology, Ferritin, chemistry.chemical_compound, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Biochemistry, biology.protein, medicine, Pathogen, Intracellular, Oxidative stress, Bacteria
Abstract

Iron is an essential nutriment for almost all forms of life, from bacteria to humans. Despite its key role in living organisms, iron becomes toxic at high concentrations. In the body, to circumvent this toxicity, almost all the intracellular iron is bound to proteins (especially to ferritin, a protein able to bind up to 4000 atoms of iron) and a small proportion (0.2% to 3%) to low molecular weight ligands (less than 2 kDa) constituting a free iron pool able to ensure the traffic of intracellular iron. A number of small molecules (citrate, phosphate, phospholipid, polypeptide) able to chelate iron, with variable affinities, have been known for a long time. In 2010, two teams have identified new mammal endogen chelators able to bind iron with similar chemical properties as bacterial siderophores. Recently, a few publications emphasized that most of the free iron present in the body cells is indeed linked to these siderophores, which play a key role in infected-host protection mechanisms during bacterial infections, through iron homeostasis and oxidative stress regulation.

Published
2015

36. Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines

Author

Anne Beauvais, Benoit Briard, Jean-Paul Latgé, Gaëtan L. A. Mislin, Virginie Lair, Beatrix E. Lechner, Marie-Christine Prévost, Hubertus Haas, Perrine Bomme, Aspergillus, Institut Pasteur [Paris], Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Microscopie ultrastructurale (plate-forme), Innsbruck Medical University [Austria] (IMU), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche de Chimie Paris (IRCP), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Research in the Aspergillus Unit of JP Latgé was supported by the Association Vaincre La Mucoviscidose (RF20140501052/1/1/141). B.E. Lechner and H. Haas were supported by the FWF project 1346-B21., Institut Pasteur [Paris] (IP), and Innsbruck Medical University = Medizinische Universität Innsbruck (IMU)

Subjects
Iron, medicine.disease_cause, Redox, Article, Aspergillus fumigatus, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, Pyocyanin, Superoxides, medicine, Mode of action, skin and connective tissue diseases, Reactive nitrogen species, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Multidisciplinary, biology, 030306 microbiology, Pseudomonas aeruginosa, Microbiota, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Reactive Nitrogen Species, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biochemistry, chemistry, Phenazines, Oxidation-Reduction, Function (biology)
Abstract

The opportunistic fungal pathogen Aspergillus fumigatus is increasingly found as a coinfecting agent along with Pseudomonas aeruginosa in cystic fibrosis patients. Amongst the numerous molecules secreted by P. aeruginosa during its growth, phenazines constitute a major class. P. aeruginosa usually secreted four phenazines, pyocyanin (PYO), phenazine-1-carboxamide (PCN), 1-hydroxyphenazine (1-HP) and phenazine-1-carboxylic acid (PCA). These phenazines inhibited the growth of A. fumigatus but the underlying mechanisms and the impact of these four phenazines on A. fumigatus biology were not known. In the present study, we analyzed the functions of the four phenazines and their mode of action on A. fumigatus. All four phenazines showed A. fumigatus growth inhibitory effects by inducing production of reactive oxygen species (ROS), specifically O2·− and reactive nitrogen species (RNS), ONOO−. A. fumigatus Sod2p was the major factor involved in resistance against the ROS and RNS induced by phenazines. Sub-inhibitory concentrations of PYO, PCA and PCN promote A. fumigatus growth by an independent iron-uptake acquisition. Of the four phenazines 1-HP had a redox-independent function; being able to chelate metal ions 1-HP induced A. fumigatus iron starvation. Our data show the fine-interactions existing between A. fumigatus and P. aeruginosa, which can lead to stimulatory or antagonistic effects.

Published
2015

37. Deciphering Protein Dynamics of the Siderophore Pyoverdine Pathway in Pseudomonas aeruginosa

Author

Guillon, L. (Laurent), Altenburger, S. (Stephan), Graumann, Peter L., Schalk, I. (Isabelle), Meijler, Michael M. (editor), Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
Siderophore, Iron, lcsh:Medicine, Biology, Bacterial cell structure, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Secretion, lcsh:Science, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Pyoverdine, 030306 microbiology, lcsh:R, Cell Polarity, Fluorescence recovery after photobleaching, Periplasmic space, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Fusion protein, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Biochemistry, Membrane protein, Pseudomonas aeruginosa, lcsh:Q, Oligopeptides, Metabolic Networks and Pathways, Research Article, Fluorescence Recovery After Photobleaching
Abstract

Pseudomonas aeruginosa produces the siderophore, pyoverdine (PVD), to obtain iron. Siderophore pathways involve complex mechanisms, and the machineries responsible for biosynthesis, secretion and uptake of the ferri-siderophore span both membranes of Gram-negative bacteria. Most proteins involved in the PVD pathway have been identified and characterized but the way the system functions as a whole remains unknown. By generating strains expressing fluorescent fusion proteins, we show that most of the proteins are homogeneously distributed throughout the bacterial cell. We also studied the dynamics of these proteins using fluorescence recovery after photobleaching (FRAP). This led to the first diffusion coefficients ever determined in P. aeruginosa. Cytoplasmic and periplamic diffusion appeared to be slower than in Escherichia coli but membrane proteins seemed to behave similarly in the two species. The diffusion of cytoplasmic and periplasmic tagged proteins involved in the PVD pathway was dependent on the interaction network to which they belong. Importantly, the TonB protein, motor of the PVD-Fe uptake process, was mostly immobile but its mobility increased substantially in the presence of PVD-Fe.

Published
2013

38. Resistance to a Rhabdovirus (VHSV) in Rainbow Trout: Identification of a Major QTL Related to Innate Mechanisms

Author

M. Dorson, Nicolas Dechamp, Corinne Torhy, Pierre Boudinot, Stéphane Mauger, Caroline Hervet, Carine Genet, Céline Ciobotaru, Edwige Quillet, Eloi R. Verrier, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), European Community (IFOP), French Ministry of Research [2004/190], European Community's SeventhFramework Programme (FP7), Research Infrastructures action [FP7-228394], Animal Genetics and Animal Health Divisions of INRA, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), and Quillet, Edwige

Subjects
Male, Aquaculture, Virus Replication, Tissue Culture Techniques, Hemorrhagic Septicemia, Viral, Animal Breeding, Animal Management, Genetics, 0303 health sciences, Novirhabdovirus, trout, Genome, Multidisciplinary, biology, qtl, Homozygote, Chromosome Mapping, Agriculture, 04 agricultural and veterinary sciences, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Survival Rate, Trout, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Veterinary Diseases, Oncorhynchus mykiss, fish, Medicine, Female, Fish Farming, rhabdovirus, Ichthyology, Research Article, Genotype, Science, Quantitative Trait Loci, Quantitative trait locus, Selective breeding, 03 medical and health sciences, Animals, 14. Life underwater, Biology, Gene, 030304 developmental biology, Veterinary Virology, biology.organism_classification, Immunity, Innate, Genetic architecture, Genetics of Disease, 040102 fisheries, Doubled haploidy, 0401 agriculture, forestry, and fisheries, Veterinary Science, Rainbow trout, Animal Genetics, Zoology, truite arc en ciel
Abstract

Chantier qualité GA; Health control is a major issue in animal breeding and a better knowledge of the genetic bases of resistance to diseases is needed in farm animals including fish. The detection of quantitative trait loci (QTL) will help uncovering the genetic architecture of important traits and understanding the mechanisms involved in resistance to pathogens. We report here the detection of QTL for resistance to Viral Haemorrhagic Septicaemia Virus (VHSV), a major threat for European aquaculture industry. Two induced mitogynogenetic doubled haploid F2 rainbow trout (Oncorhynchus mykiss) families were used. These families combined the genome of susceptible and resistant F0 breeders and contained only fully homozygous individuals. For phenotyping, fish survival after an immersion challenge with the virus was recorded, as well as in vitro virus replication on fin explants. A bidirectional selective genotyping strategy identified seven QTL associated to survival. One of those QTL was significant at the genome-wide level and largely explained both survival and viral replication in fin explants in the different families of the design (up to 65% and 49% of phenotypic variance explained respectively). These results evidence the key role of innate defence in resistance to the virus and pave the way for the identification of the gene(s) responsible for resistance. The identification of a major QTL also opens appealing perspectives for selective breeding of fish with improved resistance.

Published
2013

39. Genetic Resistance to Rhabdovirus Infection in Teleost Fish Is Paralleled to the Derived Cell Resistance Status

Author

Corinne Tohry, Christelle Langevin, Armel Houel, Eloi R. Verrier, Pierre Boudinot, Edwige Quillet, Vincent Ducrocq, Abdenour Benmansour, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Unité de recherche Virologie et Immunologie Moléculaires (VIM), and Boudinot, Pierre

Subjects
Applied Microbiology, Fish Diseases, 0302 clinical medicine, Interferon, Genetics, 0303 health sciences, Multidisciplinary, biology, Fishes, genetic factor, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Innate Immunity, 3. Good health, Host-Pathogen Interaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Veterinary Diseases, Medicine, Disease Susceptibility, Viral disease, rhabdovirus, Ichthyology, Research Article, medicine.drug, Science, Mechanisms of Resistance and Susceptibility, Immunology, Major histocompatibility complex, Microbiology, Virus, Cell Line, 03 medical and health sciences, Virology, Rhabdoviridae Infections, Genetic predisposition, medicine, resistance, Animals, Biology, Immunity to Infections, 030304 developmental biology, Immunity, Immune Defense, viral disease, Veterinary Virology, biology.organism_classification, Isogenic human disease models, biology.protein, Microbial genetics, Veterinary Science, Viral hemorrhagic septicemia, Interferons, Zoology, 030215 immunology
Abstract

Chantier qualité GA; Genetic factors of resistance and predisposition to viral diseases explain a significant part of the clinical variability observed within host populations. Predisposition to viral diseases has been associated to MHC haplotypes and T cell immunity, but a growing repertoire of innate/intrinsic factors are implicated in the genetic determinism of the host susceptibility to viruses. In a long-term study of the genetics of host resistance to fish rhabdoviruses, we produced a collection of double-haploid rainbow trout clones showing a wide range of susceptibility to Viral Hemorrhagic Septicemia Virus (VHSV) waterborne infection. The susceptibility of fibroblastic cell lines derived from these clonal fish was fully consistent with the susceptibility of the parental fish clones. The mechanisms determining the host resistance therefore did not associate with specific host immunity, but rather with innate or intrinsic factors. One cell line was resistant to rhabdovirus infection due to the combination of an early interferon IFN induction - that was not observed in the susceptible cells - and of yet unknown factors that hamper the first steps of the viral cycle. The implication of IFN was well consistent with the wide range of resistance of this genetic background to VSHV and IHNV, to the birnavirus IPNV and the orthomyxovirus ISAV. Another cell line was even more refractory to the VHSV infection through different antiviral mechanisms. This collection of clonal fish and isogenic cell lines provides an interesting model to analyze the relative contribution of antiviral pathways to the resistance to different viruses.

Published
2012

40. An efflux pump is involved in secretion of newly synthesized siderophore by

Author

Hannauer, Mélissa, Yeterian, Emilie, Martin, Lois W., Lamont, Iain L., Schalk, Isabelle, Ecole Supérieure de Biotechnologie de Strasbourg (ESBS), and Université de Strasbourg (UNISTRA)

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Published
2010

41. The ferrichrome uptake pathway in Pseudomonas aeruginosa involves an iron release mechanism with acylation of the siderophore and recycling of the modified desferrichrome

Author

Yaniv Barda, Gaëtan L. A. Mislin, Isabelle J. Schalk, Abraham Shanzer, Mélissa Hannauer, Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
Siderophore, Acylation, Iron, Physiology and Metabolism, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, medicine, Inner membrane, Molecular Biology, Escherichia coli, 030304 developmental biology, Ferrichrome, 0303 health sciences, Pyoverdine, 030306 microbiology, Pseudomonas aeruginosa, Permease, Membrane Transport Proteins, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, chemistry, Bacterial outer membrane, Metabolic Networks and Pathways
Abstract

The uptake of iron into Pseudomonas aeruginosa is mediated by two major siderophores produced by the bacterium, pyoverdine and pyochelin. The bacterium is also able of utilize several heterologous siderophores of bacterial or fungal origin. In this work, we have investigated the iron uptake in P. aeruginosa PAO1 by the heterologous ferrichrome siderophore. 55 Fe uptake assays showed that ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter. Moreover, we demonstrate that like in the uptake of ferripyoverdine and ferripyochelin, the energy required for both pathways of ferrichrome uptake is provided by the inner membrane protein TonB1. Desferrichrome- 55 Fe uptake in P. aeruginosa was also dependent on the expression of the permease FiuB, suggesting that this protein is the inner membrane transporter of the ferrisiderophore. A biomimetic fluorescent analogue of ferrichrome, RL1194, was used in vivo to monitor the kinetics of iron release from ferrichrome in P. aeruginosa in real time. This dissociation involves acylation of ferrichrome and its biomimetic analogue RL1194 and recycling of both modified siderophores into the extracellular medium. FiuC, an N -acetyltransferase, is certainly involved in this mechanism of iron release, since its mutation abolished desferrichrome- 55 Fe uptake. The acetylated derivative reacts with iron in the extracellular medium and is able to be taken up again by the cells. All these observations are discussed in light of the current knowledge concerning ferrichrome uptake in P. aeruginosa and in Escherichia coli .

Published
2010

42. FpvA bound to non-cognate pyoverdines: molecular basis of siderophore recognition by an iron transporter

Author

Franc Pattus, Valérie A. Geoffroy, Jason Greenwald, Mirella Nader, Christelle Gruffaz, Hervé Celia, Isabelle J. Schalk, Jean Marie Meyer, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire, génomique, microbiologie (GMGM), Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I, and Celia, Herve

Subjects
Siderophore, Iron, Siderophores, Plasma protein binding, Biology, Ligands, Microbiology, FpvA, Substrate Specificity, 03 medical and health sciences, chemistry.chemical_compound, Protein structure, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Binding site, Molecular Biology, 030304 developmental biology, 0303 health sciences, Pyoverdine, 030306 microbiology, pyoverdine, Circular Dichroism, Transporter, Gene Expression Regulation, Bacterial, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Protein Structure, Tertiary, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Biochemistry, Pseudomonas aeruginosa, Ferric, Oligopeptides, Bacteria, medicine.drug, Bacterial Outer Membrane Proteins, Protein Binding
Abstract

International audience; The first step in the specific uptake of iron via siderophores in Gram-negative bacteria is the recognition and binding of a ferric siderophore by its cognate receptor. We investigated the molecular basis of this event through structural and biochemical approaches. FpvA, the pyoverdine-Fe transporter from Pseudomonas aeruginosa ATCC 15692 (PAO1 strain), is able to transport ferric-pyoverdines originating from other species, whereas most fluorescent pseudomonads are only able to use the one they produce among the more than 100 known different pyoverdines. We solved the structure of FpvA bound to non-cognate pyoverdines of high- or low-affinity and found a close correlation between receptor-ligand structure and the measured affinities. The structure of the first amino acid residues of the pyoverdine chain distinguished the high- and low-affinity binders while the C-terminal portion of the pyoverdines, often cyclic, does not appear to contribute extensively to the interaction between the siderophore and its transporter. The specificity of the ferric-pyoverdine binding site of FpvA is conferred by the structural elements common to all ferric-pyoverdines, i.e. the chromophore, iron, and its chelating groups.

Published
2009

43. The Pseudomonas aeruginosa Pyochelin-Iron Uptake Pathway and Its Metal Specificity

Author

Isabelle J. Schalk, Gaëtan L. A. Mislin, Armelle Braud, Mélissa Hannauer, Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
inorganic chemicals, Siderophore, Iron, Receptors, Cell Surface, Genetics and Molecular Biology, Biology, Microbiology, Metal, 03 medical and health sciences, chemistry.chemical_compound, Phenols, Extracellular, Chelation, Molecular Biology, 030304 developmental biology, 0303 health sciences, 030306 microbiology, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Fluorescence, Thiazoles, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, chemistry, Metals, visual_art, Pseudomonas aeruginosa, Pseudomonadales, visual_art.visual_art_medium, Bacterial Outer Membrane Proteins, Protein Binding, Signal Transduction, Nuclear chemistry, Pseudomonadaceae
Abstract

Pyochelin (Pch) is one of the two major siderophores produced and secreted by Pseudomonas aeruginosa PAO1 to assimilate iron. It chelates iron in the extracellular medium and transports it into the cell via a specific outer membrane transporter, FptA. We used the fluorescent properties of Pch to show that this siderophore chelates, in addition to Fe 3+ albeit with substantially lower affinities, Ag + , Al 3+ , Cd 2+ , Co 2+ , Cr 2+ , Cu 2+ , Eu 3+ , Ga 3+ , Hg 2+ , Mn 2+ , Ni 2+ , Pb 2+ , Sn 2+ , Tb 3+ , Tl + , and Zn 2+ . Surprisingly, the Pch complexes with all these metals bound to FptA with affinities in the range of 10 nM to 4.8 μM (the affinity of Pch-Fe is 10 nM) and were able to inhibit, with various efficiencies, Pch- 55 Fe uptake in vivo. We used inductively coupled plasma atomic emission spectrometry to follow metal uptake by P. aeruginosa . Energy-dependent metal uptake, in the presence of Pch, was efficient only for Fe 3+ . Co 2+ , Ga 3+ , and Ni 2+ were also transported, but the uptake rates were 23- to 35-fold lower than that for Fe 3+ . No uptake was seen for all the other metals. Thus, cell surface FptA has broad metal specificity at the binding stage but is much more selective for the metal uptake process. This uptake pathway does not appear to efficiently assimilate any metal other than Fe 3+ .

Published
2009

44. Pseudomonas fluorescens CHA0 Produces Enantio-pyochelin, the Optical Antipode of the Pseudomonas aeruginosa Siderophore Pyochelin

Author

Paul Majcherczyk, Zeb A. Youard, Cornelia Reimmann, Isabelle J. Schalk, Gaëtan L.A. Mislin, Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)

Subjects
Siderophore, Stereochemistry, Siderophores, Pseudomonas fluorescens, medicine.disease_cause, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Isomerism, Phenols, medicine, Cysteine, Molecular Biology, Cysteine metabolism, 030304 developmental biology, 0303 health sciences, biology, Molecular Structure, 030306 microbiology, Pseudomonas aeruginosa, Thiazoline, Diastereomer, Cell Biology, Gene Expression Regulation, Bacterial, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, biology.organism_classification, Chiral column chromatography, Thiazoles, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Salicylic Acid
Abstract

The siderophore pyochelin is made by a thiotemplate mechanism from salicylate and two molecules of cysteine. In Pseudomonas aeruginosa, the first cysteine residue is converted to its D-isoform during thiazoline ring formation whereas the second cysteine remains in its L-configuration, thus determining the stereochemistry of the two interconvertible pyochelin diastereoisomers as 4 ′R, 2 ″R, 4 ″R (pyochelin I) and 4 ′R, 2 ″S, 4 ″R (pyochelin II). Pseudomonas fluorescens CHA0 was found to make a different stereoisomeric mixture, which promoted growth under iron limitation in strain CHA0 and induced the expression of its biosynthetic genes, but was not recognized as a siderophore and signaling molecule by P. aeruginosa. Reciprocally, pyochelin promoted growth and induced pyochelin gene expression in P. aeruginosa, but was not functional in P. fluorescens. The structure of the CHA0 siderophore was determined by mass spectrometry, thin-layer chromatography, NMR, polarimetry, and chiral HPLC as enantio-pyochelin, the optical antipode of the P. aeruginosa siderophore pyochelin. Enantio-pyochelin was chemically synthesized and confirmed to be active in CHA0. Its potential biosynthetic pathway in CHA0 is discussed.

Published
2007

46. Biosynthesis of the pyoverdine siderophore of Pseudomonas aeruginosa involves precursors with a myristic or a myristoleic acid chain

Author

Françoise Hoegy, Patrick Wehrung, Herbert Budzikiewicz, Mélissa Hannauer, Patrick Gizzi, Mathias Schäfer, Gaëtan L. A. Mislin, Isabelle J. Schalk, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
Siderophore, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Mutant, Biophysics, Siderophores, Biology, Biochemistry, Myristic Acid, Fluorescence, Fatty Acids, Monounsaturated, 03 medical and health sciences, chemistry.chemical_compound, Sciences du Vivant [q-bio]/Autre [q-bio.OT], Biosynthesis, Structural Biology, Genetics, Pyoverdine, Peptide Synthases, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Molecular mass, Molecular Structure, Mass spectrometry, 030306 microbiology, Cell Biology, Periplasmic space, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Iron uptake, Molecular Weight, Enzyme, chemistry, Myristoleic acid, Mutation, Pseudomonas aeruginosa, Oligopeptides
Abstract

International audience; Pyoverdine I (PVDI) is the major siderophore produced by Pseudomonas aeruginosa to import iron. Biosynthesis of this chelator involves non‐ribosomal peptide synthetases and other enzymes. PvdQ is a periplasmic enzyme from the NTN hydrolase family and is involved in the final steps of PVDI biosynthesis. A pvdQ mutant produces two non‐fluorescent PVDI precursors with a higher molecular mass than PVDI. In the present study, we describe the use of mass spectrometry to determine the structure of these PVDI precursors and show that they both contain a unformed chromophore like ferribactin, and either a myristic or myristoleic chain that must be removed before PVDI is secreted into the extracellular medium.

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results