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14 results on '"PLASMODIUM-FALCIPARUM"'

1. Phosphorylation of the VAR2CSA extracellular region is associated with enhanced adhesive properties to the placental receptor CSA

Author

Dominique Dorin-Semblat, Marilou Tétard, Aurélie Claës, Jean-Philippe Semblat, Sébastien Dechavanne, Zaineb Fourati, Romain Hamelin, Florence Armand, Graziella Matesic, Sofia Nunes-Silva, Anand Srivastava, Stéphane Gangnard, Jose-Juan Lopez-Rubio, Marc Moniatte, Christian Doerig, Artur Scherf, Benoît Gamain, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National de la Transfusion Sanguine [Paris] (INTS), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Proteomics Core Facility [Lausanne, Suisse], Ecole Polytechnique Fédérale de Lausanne (EPFL), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre for Chronic Infectious and Inflammation Disease [Bundoora, VIC, Australie], Biomedical Sciences Cluster [Bundoora, VIC, Australie], School of Health and Biomedical Sciences [Bundoora, VIC, Australie], Royal Melbourne Institute of Technology University (RMIT University)-Royal Melbourne Institute of Technology University (RMIT University)-School of Health and Biomedical Sciences [Bundoora, VIC, Australie], Royal Melbourne Institute of Technology University (RMIT University)-Royal Melbourne Institute of Technology University (RMIT University), This work is supported by the French National Research Agency (ANR-16-CE11-0014-01), grants from Laboratory of Excellence GR-Ex, reference ANR-11-LABX-0051 and the French Parasitology consortium ParaFrap (ANR-11-LABX0024). The labex GR-Ex is funded by the program 'Investissements d’avenir' of the French National Research Agency, reference ANR-11-IDEX-0005-02., ANR-16-CE11-0014,STRUCT-4-PAM,Analyse structurale et fonctionnelle des processus adhésifs associés au paludisme gestationnel(2016), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), Centre for Molecular Parasitology, University of Glasgow-Wellcome Trust, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Gènes et pression artérielle (Inserm U772), Collège de France (CdF)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrée du Globule Rouge (BIGR), Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire de Biochimie de l'Ecole polytechnique (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Proteomics Core Facility, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Controle de la Proliferation Cellulaire Chez Plasmodium Falciparum, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des Interactions Hôte-Parasite, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bodescot, Myriam, Analyse structurale et fonctionnelle des processus adhésifs associés au paludisme gestationnel - - STRUCT-4-PAM2016 - ANR-16-CE11-0014 - AAPG2016 - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, Génétique et évolution des maladies infectieuses (GEMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Plasmodium, binding, Erythrocytes, Physiology, Placenta, Cell Culture Techniques, Protozoan Proteins, Biochemistry, Database and Informatics Methods, Pregnancy, Animal Cells, Red Blood Cells, Immune Physiology, Medicine and Health Sciences, Biology (General), Malaria, Falciparum, Phosphorylation, Post-Translational Modification, ComputingMilieux_MISCELLANEOUS, chondroitin sulfate, Protozoans, Immune System Proteins, Malarial Parasites, Eukaryota, Antigenic Variation, Recombinant Proteins, Enzymes, Plasmodium Falciparum, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Female, Cellular Types, Sequence Analysis, Protein Binding, Research Article, QH301-705.5, Bioinformatics, Immunology, Antigens, Protozoan, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Research and Analysis Methods, Cell Line, var genes, Sequence Motif Analysis, expression, Parasite Groups, parasitic diseases, Animals, Humans, Parasites, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Antigens, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Blood Cells, Phosphatases, Organisms, Biology and Life Sciences, Proteins, pfemp1, Cell Biology, Parasitic Protozoans, Malaria, cytoadherence, Enzymology, Parasitology, plasmodium-falciparum, Apicomplexa
Abstract

Plasmodium falciparum is the main cause of disease and death from malaria. P. falciparum virulence resides in the ability of infected erythrocytes (IEs) to sequester in various tissues through the interaction between members of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesin family to various host receptors. Here, we investigated the effect of phosphorylation of variant surface antigen 2-CSA (VAR2CSA), a member of the PfEMP1 family associated to placental sequestration, on its capacity to adhere to chondroitin sulfate A (CSA) present on the placental syncytium. We showed that phosphatase treatment of IEs impairs cytoadhesion to CSA. MS analysis of recombinant VAR2CSA phosphosites prior to and after phosphatase treatment, as well as of native VAR2CSA expressed on IEs, identified critical phosphoresidues associated with CSA binding. Site-directed mutagenesis on recombinant VAR2CSA of 3 phosphoresidues localised within the CSA-binding region confirmed in vitro their functional importance. Furthermore, using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9), we generated a parasite line in which the phosphoresidue T934 is changed to alanine and showed that this mutation strongly impairs IEs cytoadhesion to CSA. Taken together, these results demonstrate that phosphorylation of the extracellular region of VAR2CSA plays a major role in IEs cytoadhesion to CSA and provide new molecular insights for strategies aiming to reduce the morbidity and mortality of PM., Placental sequestration of malaria-infected erythrocytes is mediated by the interaction between parasite VAR2CSA and the placental receptor chondroitin sulfate A; this study shows that phosphorylation of VAR2CSA plays a major role in this process, with implications for protecting pregnant women and their babies against placental malaria.

Published
2019
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2. Evolution of folate biosynthesis and metabolism across algae and land plant lineages

Author

O. De Clerck, Sylvain Lespinats, Vera Gorelova, D. van der Straeten, Olivier Bastien, Fabrice Rébeillé, Universiteit Gent = Ghent University [Belgium] (UGENT), Université de Genève (UNIGE), Physiologie cellulaire et végétale (LPCV), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-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), Phycology Research Group, Laboratory of Functional Plant Biology, Universiteit Gent = Ghent University (UGENT), Université de Genève = University of Geneva (UNIGE), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Ghent University [Belgium] (UGENT), LIPID, Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
0301 basic medicine, PROTEIN, lcsh:Medicine, Tetrahydrofolate, Article, Evolution, Molecular, 03 medical and health sciences, MULTIPLE SEQUENCE ALIGNMENT, 0302 clinical medicine, GAMMA-GLUTAMYL HYDROLASES, Folic Acid, Algae, Chlorophyta, P aminobenzoate, Arabidopsis thaliana, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], lcsh:Science, THYMIDYLATE SYNTHASE, 2. Zero hunger, Multidisciplinary, Phylogenetic analysis, biology, PLASMODIUM-FALCIPARUM, lcsh:R, fungi, Biology and Life Sciences, DIHYDRONEOPTERIN TRIPHOSPHATE, food and beverages, Metabolism, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, biology.organism_classification, GENE, Yeast, Metabolic pathway, 030104 developmental biology, BRANCH, Biochemistry, Rhodophyta, Vitamin B9, Nucleic acid, ARABIDOPSIS-THALIANA, Embryophyta, lcsh:Q, SUBCELLULAR-LOCALIZATION, 030217 neurology & neurosurgery, Bacteria, P-AMINOBENZOATE
Abstract

Tetrahydrofolate and its derivatives, commonly known as folates, are essential for almost all living organisms. Besides acting as one-carbon donors and acceptors in reactions producing various important biomolecules such as nucleic and amino acids, as well as pantothenate, they also supply one-carbon units for methylation reactions. Plants along with bacteria, yeast and fungi synthesize folates de novo and therefore constitute a very important dietary source of folates for animals. All the major steps of folate biosynthesis and metabolism have been identified but only few have been genetically characterized in a handful of model plant species. The possible differences in the folate pathway between various plant and algal species have never been explored. In this study we present a comprehensive comparative study of folate biosynthesis and metabolism of all major land plant lineages as well as green and red algae. The study identifies new features of plant folate metabolism that might open new directions to folate research in plants.

Published
2019
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3. The Mitochondrial DNA (mtDNA)-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination

Author

Catherine Colas des Francs-Small, Dirk Inzé, Jonas Blomme, Michiel De Bruyne, Olivier Van Aken, Jasmien Vercruysse, Geert De Jaeger, Twiggy Van Daele, Mattias Vermeersch, Teddy Jégu, Riet De Rycke, Moussa Benhamed, Liesbeth De Milde, Nathalie Gonzalez, A. Harvey Millar, Jonah Nolf, Jelle Van Leene, Universiteit Gent = Ghent University [Belgium] (UGENT), Center for Plant Systems Biology (PSB Center), and Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB)

Subjects
0301 basic medicine, H-NS, Mitochondrial DNA, DNA repair, [SDV]Life Sciences [q-bio], Arabidopsis, Plant Science, Mitochondrion, Biology, DOUBLE-STRAND BREAKS, Genome, DNA, Mitochondrial, Mitochondrial Proteins, 03 medical and health sciences, chemistry.chemical_compound, Gene Expression Regulation, Plant, Organelle, Arabidopsis thaliana, DAMAGE RESPONSE, SNF COMPLEX, Research Articles, GENE-EXPRESSION, Genetics, PLASMODIUM-FALCIPARUM, Arabidopsis Proteins, fungi, Biology and Life Sciences, food and beverages, Cell Biology, biology.organism_classification, LEAF DEVELOPMENT, Mitochondria, BINDING-PROTEIN, 030104 developmental biology, chemistry, CHROMATIN REMODELING COMPLEXES, ARABIDOPSIS-THALIANA, Homologous recombination, DNA
Abstract

In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared with their animal counterparts, and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana. Gain-and loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development.

Published
2017
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4. Phylogeography of Toxoplasma gondii points to a South American origin

Author

Hilda Fátima de Jesus Pena, Chunlei Su, Emmanuel Paradis, Daniel Ajzenberg, Emilie Bertranpetit, Jitender P. Dubey, Aurélien Mercier, Thibaut Jombart, Sébastien Devillard, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Animal Parasitic Diseases Laboratory [Beltsville, USA], United States Department of Agriculture (USDA)-USDA Agricultural Research Service [Beltsville, Maryland], USDA-ARS : Agricultural Research Service-USDA-ARS : Agricultural Research Service, Service de Parasitologie Mycologie [CHU Limoges], CHU Limoges, Medical Research Council (MRC), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London-Faculty of Medicine-Department of Infectious Disease Epidemiology, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Université de Limoges (UNILIM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) (CNR Toxoplasmose-Toxoplasma BRC), Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Institut des Sciences de l'Evolution de Montpellier ( ISEM ), Université de Montpellier ( UM ) -Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique ( CNRS ), Animal Parasitic Diseases Laboratory, United States Department of Agriculture - USDA (USA)-Agricultural Research Service-Beltsville Agricultural research Center, Université de Limoges ( UNILIM ), Université Claude Bernard Lyon 1 ( UCBL ), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) ( CNR Toxoplasmose-Toxoplasma BRC ), Ecologie et évolution des populations, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Most recent common ancestor, [SDV]Life Sciences [q-bio], Lineage (evolution), Genes, Protozoan, Time to the most recent common ancestor (TMRCA), Cat Diseases, Genetic diversity, 0302 clinical medicine, Pandemic, OCULAR TOXOPLASMOSIS, Phylogeny, ComputingMilieux_MISCELLANEOUS, PLASMODIUM-FALCIPARUM, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, BRAZIL, 3. Good health, GENOME, Phylogeography, Infectious Diseases, SAHARAN AFRICAN ORIGIN, Toxoplasma, Life Sciences & Biomedicine, Toxoplasmosis, Microbiology (medical), Genetic Speciation, 030231 tropical medicine, Zoology, Toxoplasma gondii, Biology, TOXOPLASMA GONDII, Polymorphism, Single Nucleotide, Microbiology, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, parasitic diseases, Genetics, medicine, Animals, Humans, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, Science & Technology, Genetic Variation, Maximum likelihood phylogeny, Sequence Analysis, DNA, South America, medicine.disease, biology.organism_classification, 030104 developmental biology, Toxoplasmosis, Animal, DISTANCE, Cats, PATTERNS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, CONGENITAL TOXOPLASMOSIS
Abstract

International audience; Toxoplasma gondii, a protozoan found ubiquitously in mammals and birds, is the etiologic agent of toxoplasmosis, a disease causing substantial public health burden worldwide, including about 200,000 new cases of congenital toxoplasmosis each year. Clinical severity has been shown to vary across geographical regions, with South America exhibiting the highest burden. Unfortunately, the drivers of these heterogeneities are still poorly understood, and the geographical origin and historical spread of the pathogen worldwide are currently uncertain. A worldwide sample of 168 T. gondii isolates gathered in 13 populations was sequenced for five fragments of genes (140 single nucleotide polymorphisms from 3153bp per isolate). Phylogeny based on Maximum likelihood methods with estimation of the time to the most recent common ancestor (TMRCA) and geostatistical analyses were performed for inferring the putative origin of T. gondii. We show that extant strains of the pathogen likely evolved from a South American ancestor, around 1.5 million years ago, and reconstruct the subsequent spread of the pathogen worldwide. This emergence is much more recent than the appearance of ancestral T. gondii, believed to have taken place about 11 My ago, and follows the arrival of felids in this part of the world. We posit that an ancestral lineage of T. gondii likely arrived in South America with felids and that the evolution of oral infectivity through carnivorism and the radiation of felids in this region enabled a new strain to outcompete the ancestral lineage and undergo a pandemic radiation.

Published
2016
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5. Erythropoietin Levels Increase during Cerebral Malaria and Correlate with Heme, Interleukin-10 and Tumor Necrosis Factor-Alpha in India

Author

Esther Dalko, Nicolas Tchitchek, Laurent Pays, Fabien Herbert, Pierre-André Cazenave, Balachandran Ravindran, Shobhona Sharma, Serge Nataf, Bidyut Das, Sylviane Pied, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Indo-French Centre for the Promotion of Advanced Research (IFCPAR), Associated International Laboratory Systems Immunology and Genetics of Infectious Diseases (SIGID), Department of Biotechnology from the Ministry of Science and Technology of India (DBT), Tata Institute of Fundamental Research, IFCPAR, and College Doctoral Lille Nord de France [AAP n10]

Subjects
Male, Plasmodium, Physiology, [SDV]Life Sciences [q-bio], Protozoan Proteins, lcsh:Medicine, receptors, Biochemistry, Severity of Illness Index, Geographical Locations, Hemopexin, Immune Physiology, Medicine and Health Sciences, Post-Translational Modification, lcsh:Science, Chemokine CCL2, Innate Immune System, apoptosis, Hematology, protection, Body Fluids, Interleukin-10, Blood, Female, Cerebral Malaria, Anatomy, Research Article, Adult, Asia, Immunology, Plasmodium falciparum, Malaria, Cerebral, India, Antigens, Protozoan, Heme, Blood Plasma, Young Adult, children, cytoscape, Parasite Groups, expression, parasitic diseases, Parasitic Diseases, Humans, Hemoglobin, gene, Erythropoietin, Tumor Necrosis Factor-alpha, lcsh:R, Biology and Life Sciences, Proteins, Molecular Development, Tropical Diseases, cytokines, Malaria, Immune System, People and Places, lcsh:Q, Parasitology, falciparum-malaria, plasmodium-falciparum, Apicomplexa, Developmental Biology
Abstract

International audience; Cerebral malaria (CM) caused by Plasmodium falciparum parasites often leads to the death of infected patients or to persisting neurological sequelae despite anti-parasitic treatments. Erythropoietin (EPO) was recently suggested as a potential adjunctive treatment for CM. However diverging results were obtained in patients from Sub-Saharan countries infected with P. falciparum. In this study, we measured EPO levels in the plasma of well-defined groups of P. falciparum-infected patients, from the state of Odisha in India, with mild malaria (MM), CM, or severe non-CM (NCM). EPO levels were then correlated with biological parameters, including parasite biomass, heme, tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, interferon gamma-induced protein (IP)-10, and monocyte chemoattractant protein (MCP)-1 plasma concentrations by Spearman's rank and multiple correlation analyses. We found a significant increase in EPO levels with malaria severity degree, and more specifically during fatal CM. In addition, EPO levels were also found correlated positively with heme, TNF-alpha, IL-10, IP-10 and MCP-1 during CM. We also found a significant multivariate correlation between EPO, TNF-alpha, IL-10, IP-10 MCP-1 and heme, suggesting an association of EPO with a network of immune factors in CM patients. The contradictory levels of circulating EPO reported in CM patients in India when compared to Africa highlights the need for the optimization of adjunctive treatments according to the targeted population.

Published
2016
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6. Diversification of MIF immune regulators in aphids: link with agonistic and antagonistic interactions

Author

Géraldine Dubreuil, Didier Crochard, Jean-Christophe Simon, Emeline Deleury, Christine Coustau, Institut Sophia Agrobiotech (ISA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), INRA, CNRS, Institut Sophia Agrobiotech [Sophia Antipolis] (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST

Subjects
[SDV]Life Sciences [q-bio], Genome, Insect, Gene Expression, Genome, 0302 clinical medicine, FUNCTIONAL-CHARACTERIZATION, Phylogeny, Genetics, Macrophage migration inhibitory factor, 0303 health sciences, Aphid, Host-symbiont interactions, PLASMODIUM-FALCIPARUM, food and beverages, Biological Evolution, Invertebrate immunity, Cytokines, Host-parasite interactions, Acyrthosiphon pisum, MIGRATION INHIBITORY FACTOR, ACYRTHOSIPHON-PISUM, PEA APHID, INNATE IMMUNITY, ENDOSYMBIONTS, SEQUENCE, EXPRESSION, SECRETION, Multigene Family, Host-Pathogen Interactions, Symbiotic bacteria, Research Article, Biotechnology, Biology, Immunomodulation, 03 medical and health sciences, Immune system, Animals, Symbiosis, Gene, Macrophage Migration-Inhibitory Factors, 030304 developmental biology, Innate immune system, Computational Biology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Gene Expression Regulation, Aphids, 030217 neurology & neurosurgery
Abstract

Background The widespread use of genome sequencing provided evidences for the high degree of conservation in innate immunity signalling pathways across animal phyla. However, the functioning and evolutionary history of immune-related genes remains unknown for most invertebrate species. A striking observation coming from the analysis of the pea aphid Acyrthosiphon pisum genome is the absence of important conserved genes known to be involved in the antimicrobial responses of other insects. This reduction in antibacterial immune defences is thought to be related to their long-term association with beneficial symbiotic bacteria and to facilitate symbiont maintenance. An additional possibility to avoid elimination of mutualistic symbionts is a fine-tuning of the host immune response. To explore this hypothesis we investigated the existence and potential involvement of immune regulators in aphid agonistic and antagonistic interactions. Results In contrast to the limited antibacterial arsenal, we showed that the pea aphid Acyrthosiphon pisum expresses 5 members of Macrophage Migration Inhibitory Factors (ApMIF), known to be key regulators of the innate immune response. In silico searches for MIF members in insect genomes followed by phylogenetic reconstruction suggest that evolution of MIF genes in hemipteran species has been shaped both by differential losses and serial duplications, raising the question of the functional importance of these genes in aphid immune responses. Expression analyses of ApMIFs revealed reduced expression levels in the presence, or during the establishment of secondary symbionts. By contrast, ApMIFs expression levels significantly increased upon challenge with a parasitoid or a Gram-negative bacteria. This increased expression in the presence of a pathogen/parasitoid was reduced or missing, in the presence of facultative symbiotic bacteria. Conclusions This work provides evidence that while aphid’s antibacterial arsenal is reduced, other immune genes widely absent from insect genomes are present, diversified and differentially regulated during antagonistic or agonistic interactions. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-762) contains supplementary material, which is available to authorized users.

Published
2014
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7. Extensive inter- and intraspecific venom variation in closely related parasites targeting the same host: The case of Leptopilina parasitoids of Drosophila

Author

Julie Poulain, Jean-Luc Gatti, Caroline Anselme, Emeline Deleury, Marylène Poirié, Dominique Cazes, Dominique Colinet, Carole Azéma-Dossat, Maya Belghazi, Institut Sophia Agrobiotech (ISA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), IG, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Aix Marseille Université (AMU), Genoscope (Parasitoid venoms project), French National Research Agency (CLIMEVOL project) [ANR-08-BLAN-0231], French National Research Agency (PARATOXOSE project) [ANR-09-BLAN-0243-01], Department of Plant Health and Environment from the French National Institute for Agricultural Research (INRA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Proteomics, 0106 biological sciences, Insecta, Wasps, Leptopilina, Wasp Venoms, Venom, Generalist and specialist species, 01 natural sciences, Biochemistry, ANTIGENIC VARIATION, Intra-and interspecific variation, Heterotoma, Phylogeny, WASP PIMPLA-HYPOCHONDRIACA, Genetics, 0303 health sciences, biology, Virulence, PLASMODIUM-FALCIPARUM, Ecology, Parasitoid wasps, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, VENTURIA-CANESCENS, Insect Proteins, Drosophila, food.ingredient, Molecular Sequence Data, 010603 evolutionary biology, Host Specificity, Host-Parasite Interactions, 03 medical and health sciences, food, Phylogenetics, VIRUS-LIKE PARTICLES, Animals, Amino Acid Sequence, Molecular Biology, 030304 developmental biology, ENDOPARASITIC WASP, Venom proteins, MOLECULAR-CLONING, Host (biology), Venom Protein, biology.organism_classification, PTEROMALUS-PUPARUM HYMENOPTERA, CELLULAR IMMUNE-RESPONSE, BOULARDI HYMENOPTERA, Insect Science, Sequence Alignment
Abstract

International audience; The arms race between immune suppressive parasites that produce virulence factors and hosts that evolve resistance to these factors is suggested to be a key driver for the diversification of both partners. However, little is known regarding the diversity of virulence factors in closely related parasites or the mechanisms underlying the variation of virulence. One of the best-described model to address this issue is the interaction between Leptopilina parasitic wasps and their Drosophila hosts, in which variation of virulence is well documented. Thanks to a combined transcriptomic and proteomic approach, we have identified the main secreted proteins in the venom of Leptopilina heterotoma (Gotheron strain, 66 proteins) and of two well-characterized strains of Leptopilina boulardi, ISm and ISy (65 and 49 proteins, respectively). Results revealed significant quantitative differences in venom components between the L. boulardi strains, in agreement with their different virulence properties. Strikingly, the two related Leptopilina species did not share any abundant venom protein. The main identified proteins in L boulardi were RhoGAPs and serpins while an aspartylglucosaminidase (AGA) was found abundant in L heterotoma. The extensive quantitative variation observed between these species may be related with their use of different virulence strategies and/or to differences in their host range (specialist versus generalist). Altogether, our data suggests that parasitoid venom can quickly evolve, mainly through rapid changes in regulation of gene expression. It also evidences venom evolutionary processes largely described in other venomous animals i.e. the convergent recruitment of venom proteins between phylogenetically unrelated organisms, and the role of duplications in the emergence of multigenic families of virulence factors.

Published
2013
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8. Inhibition of p-Aminobenzoate and Folate Syntheses in Plants and Apicomplexan Parasites by Natural Product Rubreserine

Author

Jeroen Van Daele, Fabrice Rébeillé, Roland Douce, Caroline Barette, Cordelia Bisanz, Djeneb Camara, Willy E. Lambert, Esmare Human, Eric Maréchal, Marie-France Cesbron-Delauw, Renaud Dumas, Dominique Van Der Straeten, Bernice Barnard, Lyn-Marie Birkholtz, Christophe P. Stove, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Groupe Plateforme et Moyens Scientifiques et techniques communs / Centre de Criblage pour Molécules Bio-Actives (GPMS / CMBA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Toxicology, State University of Ghent, Malaria Research Group, University of Pretoria [South Africa], Laboratory of Functional Plant Biology, Ghent University [Belgium] (UGENT), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Universiteit Gent = Ghent University [Belgium] (UGENT), Region Rhone-Alpes, Ghent University [BOF09-GOA-004], Agence Nationale de la Recherche PlasmoExpress grant, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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), Genetics and Chemogenomics (GenChem), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Universiteit Gent = Ghent University (UGENT)

Subjects
0106 biological sciences, Plasmodium, one carbon metabolism, Arabidopsis thaliana, Physostigmine, Arabidopsis, plant, 01 natural sciences, Biochemistry, chemistry.chemical_compound, high troughput screening, 0303 health sciences, biology, Antiparasitic Agents, antifolate drugs, Recombinant Proteins, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Antifolate, parasite, CHORISMATE-UTILIZING ENZYMES, DE-NOVO SYNTHESIS, PLASMODIUM-FALCIPARUM, TOXOPLASMA-GONDII, AMINODEOXYCHORISMATE SYNTHASE, ANTHRANILATE SYNTHASE, 4-AMINO-4-DEOXYCHORISMATE SYNTHASE, ISOCHORISMATE SYNTHASE, GMP SYNTHETASE, GLUCOSE ESTER, Growth inhibition, 4-Aminobenzoic Acid, Toxoplasma, Aminodeoxychorismate synthase, Plasmodium falciparum, GAT-ADCS, folate, glutamine amidotransferase aminodeoxychorismate synthase, 03 medical and health sciences, Inhibitory Concentration 50, Folic Acid, pABA biosynthesis, P aminobenzoate, parasitic diseases, 4-Aminobenzoic acid, Escherichia coli, biosynthesis inhibitor, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Glutamine amidotransferase, Dose-Response Relationship, Drug, Plant Extracts, rubreserine, cofactor, Cell Biology, Antiparasitic agent, Kinetics, chemistry, Models, Chemical, Isochorismate synthase, biology.protein, Apicomplexa, metabolism, 010606 plant biology & botany, Phytotherapy
Abstract

International audience; Glutamine amidotransferase/aminodeoxychorismate synthase (GAT-ADCS) is a bifunctional enzyme involved in the synthesis of p-aminobenzoate, a central component part of folate cofactors. GAT-ADCS is found in eukaryotic organisms autonomous for folate biosynthesis, such as plants or parasites of the phylum Apicomplexa. Based on an automated screening to search for new inhibitors of folate biosynthesis, we found that rubreserine was able to inhibit the glutamine amidotransferase activity of the plant GAT-ADCS with an apparent IC(50) of about 8 μm. The growth rates of Arabidopsis thaliana, Toxoplasma gondii, and Plasmodium falciparum were inhibited by rubreserine with respective IC(50) values of 65, 20, and 1 μm. The correlation between folate biosynthesis and growth inhibition was studied with Arabidopsis and Toxoplasma. In both organisms, the folate content was decreased by 40-50% in the presence of rubreserine. In both organisms, the addition of p-aminobenzoate or 5-formyltetrahydrofolate in the external medium restored the growth for inhibitor concentrations up to the IC(50) value, indicating that, within this range of concentrations, rubreserine was specific for folate biosynthesis. Rubreserine appeared to be more efficient than sulfonamides, antifolate drugs known to inhibit the invasion and proliferation of T. gondii in human fibroblasts. Altogether, these results validate the use of the bifunctional GAT-ADCS as an efficient drug target in eukaryotic cells and indicate that the chemical structure of rubreserine presents interesting anti-parasitic (toxoplasmosis, malaria) potential.

Published
2012
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9. A novel mechanism for egress of malarial parasites from red blood cells

Author

Gladys Massiera, Catherine Braun-Breton, Laurence Berry, Manouk Abkarian, Magali Roques, Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)

Subjects
Erythrocytes, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Immunology, Plasmodium falciparum, Osmotic swelling, Video microscopy, Biology, In Vitro Techniques, 010402 general chemistry, 01 natural sciences, Biochemistry, 03 medical and health sciences, Osmotic Pressure, FALCIPARUM-INFECTED ERYTHROCYTES, STRETCHED VESICLES, INSIDE-OUT VESICULATION, Fluorescence microscope, Parasite hosting, Animals, Humans, Malaria, Falciparum, Cell Shape, 030304 developmental biology, Malarial parasites, RELEASE, 0303 health sciences, Pancreatic Elastase, PLASMODIUM-FALCIPARUM, Erythrocyte Membrane, Cell Biology, Hematology, biology.organism_classification, Virology, MEROZOITES, Elasticity, 0104 chemical sciences, Membrane, Differential interference contrast microscopy, TRANSIENT PORES, Biophysics, SHAPE CHANGES, HOST-CELL, MEMBRANE
Abstract

The culminating step of the intraerythrocytic development of Plasmodium falciparum, the causative agent of malaria, is the spectacular release of multiple invasive merozoites on rupture of the infected erythrocyte membrane. This work reports for the first time that the whole process, taking place in time scales as short as 400 milliseconds, is the result of an elastic instability of the infected erythrocyte membrane. Using high-speed differential interference contrast (DIC) video microscopy and epifluorescence, we demonstrate that the release occurs in 3 main steps after osmotic swelling of the infected erythrocyte: a pore opens in ∼ 100 milliseconds, ejecting 1-2 merozoites, an outward curling of the erythrocyte membrane is then observed, ending with a fast eversion of the infected erythrocyte membrane, pushing the parasites forward. It is noteworthy that this last step shows slight differences when infected erythrocytes are adhering. We rationalize our observations by considering that during the parasite development, the infected erythrocyte membrane acquires a spontaneous curvature and we present a subsequent model describing the dynamics of the curling rim. Our results show that sequential erythrocyte membrane curling and eversion is necessary for the parasite efficient angular dispersion and might be biologically essential for fast and numerous invasions of new erythrocytes.

Published
2011
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10. Metabolism of Folates in Plants

Author

Roland Douce, Stéphane Ravanel, Fabrice Rébeillé, CEA (Association Euratom), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)

Subjects
0106 biological sciences, Vitamin, SERINE HYDROXYMETHYLTRANSFERASE, [SDV]Life Sciences [q-bio], PRECURSOR P-AMINOBENZOATE, Biofortification, FOLIC-ACID, Biology, 01 natural sciences, Metabolic engineering, Serine, 03 medical and health sciences, chemistry.chemical_compound, GAMMA-GLUTAMYL HYDROLASES, GTP CYCLOHYDROLASE-I, NUCLEAR-MAGNETIC-RESONANCE, Purine metabolism, ONE-CARBON METABOLISM, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Methionine, PLASMODIUM-FALCIPARUM, food and beverages, Metabolism, 3. Good health, Biochemistry, chemistry, Glycine, ARABIDOPSIS-THALIANA, NEURAL-TUBE DEFECTS, 010606 plant biology & botany
Abstract

International audience; Tetrahydrofolate and its derivatives, collectively termed folates or vitamin B9, are essential cofactors for one-carbon metabolism. They transport and donate Cl-units for the synthesis of pantothenate, purines, thymidylate, serine, glycine, methionine and formylmethionyl-tRNA. Also, recent studies indicate that folates can act as electron donors in major cellular processes. Plants and many microorganisms synthesize folates de novo through a complex metabolic route that is now fully elucidated. In contrast, humans and other vertebrates lack a complete biosynthetic pathway and thus need dietary folates, of which plants are major sources. Folate deficiency is widespread in rich and developing countries and is associated with severe health problems. Supplementation of foods with synthetic folic acid and biofortification is an alternative strategy to fight folate deficiency. Encouraging pilot metabolic engineering studies in plants enabled significant enhancement of folate contents. In the next future, increasing our knowledge about the mechanisms controlling folates homeostasis in plants will provide the keys towards efficient biofortification of plant foods.

Published
2011
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11. Identification of three CCp genes in Babesia divergens: Novel markers for sexual stages parasites

Author

Thibaut Larcher, Claire A.M. Becker, Laurence Malandrin, Peter H. David, Emmanuel Bischoff, D. Depoix, Sarah Bonnet, Alain Chauvin, Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), INRA, Region Pays de Loire, Delegation Generale pour l'Armement (DGA) [22120/DSP/SREAF, 04 34 025], 'Fonds dedie Combattre les Maladies Parasitaires' (Sanofi-Aventis/Ministere de l'Enseignement Superieur et de la Recherche), AIP Bioressources, Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Expertise en Anatomie Pathologique (APEX), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Immunologie moléculaire des parasites, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Puces à ADN (Plate-Forme 2) (PF2), Institut Pasteur [Paris] (IP), and This work is part of CB's PhD thesis, which was funded by INRA and Region Pays de Loire. EB was funded by the Délégation Générale pour l’Armement (DGA nos 22120/DSP/SREAF and 04 34 025). The work also received financial support from the 'Fonds dédié Combattre les Maladies Parasitaires' (Sanofi-Aventis/Ministère de l’Enseignement Supérieur et de la Recherche). Sequencing was partially funded by AIP Bioressources.

Subjects
Genetic Markers, EXPRESSION, Plasmodium, Virulence Factors, Sexual stages, TRANSMISSION, In silico, [SDV]Life Sciences [q-bio], Molecular Sequence Data, gametocytes, Protozoan Proteins, Babesia, Genome, 030308 mycology & parasitology, CLONING, 03 medical and health sciences, Babesia divergens, parasitic diseases, Animals, Parasite hosting, Molecular Biology, Gene, 030304 developmental biology, Genetics, 0303 health sciences, Ixodes, biology, PLASMODIUM-FALCIPARUM, Sequence Analysis, DNA, DNA, Protozoan, biology.organism_classification, Virology, GENOME-SEQUENCE, LIFE-CYCLE, Sexual reproduction, PROTEIN DISULFIDE-ISOMERASE, MOSQUITO, HOMOLOG, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, CRYPTOSPORIDIUM-PARVUM, Parasitology, CCp family
Abstract

International audience; Babesia divergens, a tick-borne protozoan parasite of red blood cells, is the main agent of bovine and human babesiosis in Europe. Very few data are available concerning its life cycle and sexual reproduction inside the tick vector, Ixodes ricinus. The aim of this study was to define some markers of the B. divergens sexual stage. An in silico post-genomic approach was used to analyze genomic, transcriptomic and proteomic data and to select specific sexual stage proteins of the related apicomplexan genus Plasmodium. Three proteins, based on sequence identity between the available genomes of Plasmodium and Babesia spp., were chosen, as members of a highly conserved and apicomplexan sexual stages specific protein family (CCp) potentially involved in adhesive functions. Degenerate primers were used to amplify and clone three B. divergens orthologs (bdccp1, bdccp2, and bdccp3) corresponding to newly identified genes in this parasite. The opportunities offered by such markers to study parasite development in its vector are discussed. (C) 2010 Elsevier B.V. All rights reserved.

Published
2010
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12. Corrigendum to 'Diversity of chemical mechanisms in thioredoxin catalysis revealed by single-molecule force spectroscopy'

Author

Raul Perez-Jimenez, Jingyuan Li, Pallav Kosuri, Inmaculada Sanchez-Romero, Arun P Wiita, David Rodriguez-Larrea, Ana Chueca, Arne Holmgren, Antonio Miranda-Vizuete, Katja Becker, Seung-Hyun Cho, Jon Beckwith, Eric Gelhaye, Jean P Jacquot, Eric A Gaucher, Jose M Sanchez-Ruiz, Bruce J Berne, Julio M Fernandez, Columbia University [New York], Department of Chemistry, Universidad de Granada (UGR), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Karolinska Institutet [Stockholm], Universidad Pablo de Olavide, Justus-Liebig-Universität Gießen (JLU), Department of Microbiology and Molecular Genetics, Harvard Medical School [Boston] (HMS), Interactions Arbres-Microorganismes (IAM), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), School of Biology, and Georgia Institute of Technology [Atlanta]

Subjects
ESCHERICHIA-COLI THIOREDOXIN, 0303 health sciences, PLASMODIUM-FALCIPARUM, [SDV]Life Sciences [q-bio], 030302 biochemistry & molecular biology, REDUCED FORM, CHLAMYDOMONAS-REINHARDTII, 03 medical and health sciences, ASCORBATE OXIDASE, Structural Biology, DROSOPHILA-MELANOGASTER, REDOX POTENTIALS, ARABIDOPSIS-THALIANA, INTRAMOLECULAR ELECTRON-TRANSFER, CRYSTAL-STRUCTURES, Molecular Biology, 030304 developmental biology
Abstract

Corrigendum associated with this Article: Diversity of chemical mechanisms in thioredoxin catalysis revealed by single-molecule force spectroscopy. Nature Structural & Molecular Biology, 16 (9) 890-898. 2009 doi: 10.1038/nsmb.1627; International audience

Published
2010
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13. Antiplasmodial activities of homogentisic acid derivative protein kinase inhibitors isolated from a vanuatu marine sponge Pseudoceratina sp

Author

Arnaud Parenty, Dominique Dorin-Semblat, Dominique Laurent, Nicolas Lebouvier, Christian Doerig, Valérie Jullian, Michel Sauvain, Séverine Maurel, Isabelle Desvignes, BUNC, Pole ID, Laboratoire Insulaire du Vivant et de l'Environnement (LIVE), and Université de la Nouvelle-Calédonie (UNC)

Subjects
Plasmodium, [SDV]Life Sciences [q-bio], Pharmaceutical Science, 01 natural sciences, Psammaplysilla-Purpurea, chemistry.chemical_compound, falciparum, Vanuatu, Pseudoceratina, Brominated Metabolites, Drug Discovery, Pfnek-1, homogentisic acid derivatives, Plasmodium falciparum, lcsh:QH301-705.5, Methyltransferase, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Homogentisic Acid, chemistry.chemical_classification, biology, Kinase, Verongida Sponges, 3. Good health, Anti-Bacterial Agents, Porifera, [SDV] Life Sciences [q-bio], Chemistry, Biochemistry, Plasmodium-Falciparum, Stereochemistry, Natural-Products, Article, Antimalarials, Alkaloids, Animals, 14. Life underwater, Homogentisic acid, Protein kinase A, IC50, Protein Kinase Inhibitors, Enzyme Assays, 010405 organic chemistry, Bromotyrosine-Derived Metabolites, biology.organism_classification, In vitro, Malaria, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Sponge, Enzyme, lcsh:Biology (General), chemistry
Abstract

As part of our search for new antimalarial drugs in South Pacific marine sponges, we have looked for inhibitors of Pfnek-1, a specific protein kinase of Plasmodium falciparum. On the basis of promising activity in a preliminary screening, the ethanolic crude extract of a new species of Pseudoceratina collected in Vanuatu was selected for further investigation. A bioassay-guided fractionation led to the isolation of a derivative of homogentisic acid [methyl (2,4-dibromo-3,6-dihydroxyphenyl)acetate, 4a] which inhibited Pfnek-1 with an IC(50) around 1.8 muM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC(50) = 12 muM). From the same sponge, we isolated three known compounds [11,19-dideoxyfistularin-3 (1), 11-deoxyfistularin-3 (2) and dibromo-verongiaquinol (3)] which were inactive against Pfnek-1. Synthesis and biological evaluation of some derivatives of 4a are reported.

Published
2009

14. Malaria parasites in mosquitoes : laboratory models, evolutionary temptation and the real world

Author

Christophe Boëte, Génétique et évolution des maladies infectieuses (GEMI), and Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD [France-Sud])

Subjects
Plasmodium berghei, media_common.quotation_subject, Anopheles gambiae, Zoology, melanization, virus, Temptation, Host-Parasite Interactions, Evolution, Molecular, sephadex beads, Immune system, Immunity, Anopheles, parasitic diseases, medicine, Animals, Humans, Laboratory of Entomology, media_common, Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, anopheles-gambiae, Plasmodium falciparum, biology.organism_classification, medicine.disease, Laboratorium voor Entomologie, immunity, Insect Vectors, Malaria, Rats, Disease Models, Animal, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Gene Expression Regulation, Vector (epidemiology), Parasitology, plasmodium-falciparum, vector, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

A recent study describing the effect of Plasmodium berghei infection on some Anopheles gambiae immune genes demonstrates that P. berghei is responsible for the upregulation of several genes involved in the immune response that affect parasitic development differently during the ookinete-to-oocyst developmental transition. It is important to question the relevance of such results, which are based on a laboratory model system, when discussing host-parasite interactions and, especially, the development of novel control strategies for malaria.

Published
2005
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