Search

Your search keyword '"Biran, Marc"' showing total 187 results
Start Over Author "Biran, Marc"
187 results on '"Biran, Marc"'

2. Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker‐free gene editing in Trypanosoma and Leishmania

Author

Asencio, Corinne, primary, Hervé, Perrine, additional, Morand, Pauline, additional, Oliveres, Quentin, additional, Morel, Chloé Alexandra, additional, Prouzet‐Mauleon, Valérie, additional, Biran, Marc, additional, Monic, Sarah, additional, Bonhivers, Mélanie, additional, Robinson, Derrick Roy, additional, Ouellette, Marc, additional, Rivière, Loïc, additional, Bringaud, Frédéric, additional, and Tetaud, Emmanuel, additional

Published
2024
Full Text
View/download PDF

4. Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker-free gene editing in Trypanosoma and Leishmania

Author

Asencio, Corinne, primary, Herve, Perrine, additional, Morand, Pauline, additional, Oliveres, Quentin, additional, Morel, Chloe Alexandra, additional, Prouzet-Mauleon, Valerie, additional, Biran, Marc, additional, Monic, Sarah, additional, Bonhivers, Melanie, additional, Robinson, Derrick Roy, additional, Ouellette, Marc, additional, Riviere, Loic, additional, Bringaud, Frederic, additional, and Tetaud, Emmanuel, additional

Published
2023
Full Text
View/download PDF

5. Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation

Author

Taleva, Gergana, primary, Husová, Michaela, additional, Panicucci, Brian, additional, Hierro-Yap, Carolina, additional, Pineda, Erika, additional, Biran, Marc, additional, Moos, Martin, additional, Šimek, Petr, additional, Butter, Falk, additional, Bringaud, Frédéric, additional, and Zíková, Alena, additional

Published
2023
Full Text
View/download PDF

9. Confining Trypanosoma brucei in emulsion droplets reveals population variabilities in division rates and improves in vitro cultivation

Author

Allmann, Stefan, Wargnies, Marion, Plazolles, Nicolas, Cahoreau, Edern, Biran, Marc, Morand, Pauline, Pineda, Erika, Kulyk, Hanna, Asencio, Corinne, Villafraz, Oriana, Rivière, Loïc, Tetaud, Emmanuel, Rotureau, Brice, Mourier, Arnaud, Portais, Jean-Charles, Dé Ric Bringaud, Fré, Oldenburg, Simone, Buisson, Lionel, Beneyton, Thomas, Pekin, Deniz, Thonnus, Magali, Bringaud, Frédéric, Baret, Jean-Christophe, Microbiologie Fondamentale et Pathogénicité [Bordeaux] (MFP), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)

Subjects
Science, Microfluidics, Trypanosoma brucei brucei, Cell, Population, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Trypanosoma brucei, 01 natural sciences, Article, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Droplet size, 030304 developmental biology, 0303 health sciences, education.field_of_study, Multidisciplinary, Lab-on-a-chip, Host (biology), 010401 analytical chemistry, Tsetse fly, biology.organism_classification, In vitro, 0104 chemical sciences, Cell biology, Parasite biology, medicine.anatomical_structure, Biological Variation, Population, Medicine, Emulsions, Single-Cell Analysis, Emulsion droplet, Cell Division
Abstract

Trypanosome parasites are infecting mammals in Sub-Saharan Africa and are transmitted between hosts through bites of the tsetse fly. The transmission from the insect vector to the mammal host causes a number of metabolic and physiological changes. A fraction of the population continuously adapt to the immune system of the host, indicating heterogeneity at the population level. Yet, the cell to cell variability in populations is mostly unknown. We develop here an analytical method for quantitative measurements at the single cell level based on encapsulation and cultivation of single-cell Trypanosoma brucei in emulsion droplets. We first show that mammalian stage trypanosomes survive for several hours to days in droplets, with an influence of droplet size on both survival and growth. We unravel various growth patterns within a population and find that droplet cultivation of trypanosomes results in 10-fold higher cell densities of the highest dividing cell variants compared to standard cultivation techniques. Some variants reach final cell titers in droplets closer to what is observed in nature than standard culture, of practical interest for cell production. Droplet microfluidics is therefore a promising tool for trypanosome cultivation and analysis with further potential for high-throughput single cell trypanosome analysis.

Published
2021
Full Text
View/download PDF

18. Glycerol suppresses glucose consumption in trypanosomes through metabolic contest

Author

Allmann, Stefan, primary, Wargnies, Marion, additional, Plazolles, Nicolas, additional, Cahoreau, Edern, additional, Biran, Marc, additional, Morand, Pauline, additional, Pineda, Erika, additional, Kulyk, Hanna, additional, Asencio, Corinne, additional, Villafraz, Oriana, additional, Rivière, Loïc, additional, Tetaud, Emmanuel, additional, Rotureau, Brice, additional, Mourier, Arnaud, additional, Portais, Jean-Charles, additional, and Bringaud, Frédéric, additional

Published
2021
Full Text
View/download PDF

19. Procyclic trypanosomes recycle glucose catabolites and TCA cycle intermediates to stimulate growth in the presence of physiological amounts of proline

Author

Villafraz, Oriana, Biran, Marc, Pineda, Erika, Plazolles, Nicolas, Cahoreau, Edern, Ornitz Oliveira Souza, Rodolpho, Thonnus, Magali, Allmann, Stefan, Tetaud, Emmanuel, Rivière, Loïc, Silber, Ariel M., Barrett, Michael P., Zíková, Alena, Boshart, Michael, Portais, Jean-Charles, Bringaud, Frédéric, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade de São Paulo = University of São Paulo (USP), Ludwig-Maximilians-Universität München (LMU), University of Glasgow, Institute of Parasitology [České Budějovice] (BIOLOGY CENTRE CAS), Biology Centre of the Czech Academy of Sciences (BIOLOGY CENTRE CAS), Czech Academy of Sciences [Prague] (CAS)-Czech Academy of Sciences [Prague] (CAS), Geroscience and rejuvenation research center (RESTORE), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux, CNRS, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), ANR-15-CE15-0025,GLYCONOV,Voies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomes(2015), ANR-19-CE15-0004,AdipoTryp,Interactions métaboliques entre les adipocytes et les trypanosomes, un nouveau paradigme pour les trypanosomoses(2019), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), Université de Bordeaux (UB), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade de São Paulo (USP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-15-CE15-002501, ANR19-CE15-0004-01, Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), VIAUD, Karine, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Voies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomes - - GLYCONOV2015 - ANR-15-CE15-0025 - AAPG2015 - VALID, Interactions métaboliques entre les adipocytes et les trypanosomes, un nouveau paradigme pour les trypanosomoses - - AdipoTryp2019 - ANR-19-CE15-0004 - AAPG2019 - VALID, and Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID

Subjects
Metabolic Processes, Pyruvate, Trypanosoma, Proline, Tsetse Flies, QH301-705.5, Physiology, Citric Acid Cycle, Trypanosoma brucei brucei, Excretion, Carbohydrates, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Biochemistry, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Glucose Metabolism, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Biology (General), Amino Acids, Protozoans, Alanine, Organic Compounds, Organic Chemistry, Monosaccharides, fungi, Organisms, Chemical Compounds, Biology and Life Sciences, Eukaryota, Proteins, Cyclic Amino Acids, RC581-607, Ketones, Parasitic Protozoans, Insect Vectors, Chemistry, Glucose, Trypanosomiasis, African, Metabolism, Aliphatic Amino Acids, Physical Sciences, Carbohydrate Metabolism, RNA Interference, Immunologic diseases. Allergy, Physiological Processes, Oxidation-Reduction, Acids, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article
Abstract

Trypanosoma brucei, a protist responsible for human African trypanosomiasis (sleeping sickness), is transmitted by the tsetse fly where the procyclic forms of the parasite develop in the proline-rich (1–2 mM) and glucose-depleted digestive tract. Proline is essential for the midgut colonization of the parasite in the insect vector, however other carbon sources could be available and used to feed its central metabolism. Here we show that procyclic trypanosomes can consume and metabolize metabolic intermediates, including those excreted from glucose catabolism (succinate, alanine and pyruvate), with the exception of acetate, which is the ultimate end-product excreted by the parasite. Among the tested metabolites, tricarboxylic acid (TCA) cycle intermediates (succinate, malate and α-ketoglutarate) stimulated growth of the parasite in the presence of 2 mM proline. The pathways used for their metabolism were mapped by proton-NMR metabolic profiling and phenotypic analyses of thirteen RNAi and/or null mutants affecting central carbon metabolism. We showed that (i) malate is converted to succinate by both the reducing and oxidative branches of the TCA cycle, which demonstrates that procyclic trypanosomes can use the full TCA cycle, (ii) the enormous rate of α-ketoglutarate consumption (15-times higher than glucose) is possible thanks to the balanced production and consumption of NADH at the substrate level and (iii) α-ketoglutarate is toxic for trypanosomes if not appropriately metabolized as observed for an α-ketoglutarate dehydrogenase null mutant. In addition, epimastigotes produced from procyclics upon overexpression of RBP6 showed a growth defect in the presence of 2 mM proline, which is rescued by α-ketoglutarate, suggesting that physiological amounts of proline are not sufficient per se for the development of trypanosomes in the fly. In conclusion, these data show that trypanosomes can metabolize multiple metabolites, in addition to proline, which allows them to confront challenging environments in the fly., Author summary In the midgut of its insect vector, trypanosomes rely on proline to feed their energy metabolism. However, the availability of other potential carbon sources that can be used by the parasite is currently unknown. Here we show that tricarboxylic acid (TCA) cycle intermediates, i.e. succinate, malate and α-ketoglutarate, stimulate growth of procyclic trypanosomes incubated in a medium containing 2 mM proline, which is in the range of the amounts measured in the midgut of the fly. Some of these additional carbon sources are needed for the development of epimastigotes, which differentiate from procyclics in the midgut of the fly, since their growth defect observed in the presence of 2 mM proline is rescued by addition of α-ketoglutarate. In addition, we have implemented new approaches to study a poorly explored branch of the TCA cycle converting malate to α-ketoglutarate, which was previously described as non-functional in the parasite, regardless of the glucose levels available. The discovery of this branch reveals that a full TCA cycle can operate in procyclic trypanosomes. Our data broaden the metabolic potential of trypanosomes and pave the way for a better understanding of the parasite’s metabolism in various organ systems of the tsetse fly, where it develops.

Published
2021
Full Text
View/download PDF

21. Mitochondrial energetics is impaired in vivo in aged skeletal muscle

Author

Gouspillou, Gilles, Bourdel-Marchasson, Isabelle, Rouland, Richard, Calmettes, Guillaume, Biran, Marc, Deschodt-Arsac, Véronique, Miraux, Sylvain, Thiaudiere, Eric, Pasdois, Philippe, Detaille, Dominique, Franconi, Jean-Michel, Babot, Marion, Trézéguet, Véronique, Arsac, Laurent, and Diolez, Philippe

Published
2014
Full Text
View/download PDF

22. Vitamin A deficiency in rats induces anatomic and metabolic changes comparable with those of neurodegenerative disorders

Author

Rahab, Nadirah Ghenimi, Beauvieux, Marie-Christine, Biran, Marc, Pallet, Veronique, Higueret, Paul, and Gallis, Jean-Louis

Subjects
Vitamin A deficiency -- Research, Nervous system -- Degeneration, Nervous system -- Risk factors, Food/cooking/nutrition
Abstract

Anatomic and metabolic changes in central nervous system induced by 14 wk of vitamin A deprivation (VAD) were monitored and quantified in rats. In vivo brain magnetic resonance imaging (4.7T) was performed at 5, 7, 9, 11, and 14 wk of each diet after weaning in the following: 1) VAD group; 2) control pair-fed group; and 3) control group that consumed the diet ad libitum (1.15 [micro]g retinol/g diet). After 14 wk, high-resolution magic angle spinning proton NMR spectroscopy (11.7T) was performed on small samples of cortex, hippocampus, and striatum. Serum retinol concentrations remained stable and cerebral volume (CV) increased as a linear function of body weight in the ad libitum group ([R.sup.2] = 0.78; P= 0.047) and pair-fed controls ([R.sup.2] = 0.78; P = 0.046). In VAD rats, retinol decreased from the onset of deprivation (2.2 [+ or -] 0.14 [micro]mol/L) to reach 0.3 [+ or -] 0.13 [micro]mol/L at wk 5, followed by a stopping of body weight gain from wk 7. In VAD rats, the CV decreased from wk 5 and reached a value 11% lower than that of the control group (P < 0.001) at wk 14 and was correlated with retinol status ([R.sup.2] = 0.99; P = 0.002). The VAD hippocampal volume decreased beginning at wk 9 and was 22% lower than that of the control group at wk 14 (P < 0.001). Compared with the control, VAD led to lower N acetyl aspartate: creatine+phosphocreatine (Cr) in cortex (-36%), striatum (-22%), and hippocampus (-19%) and higher myoinositol:Cr in cortex (+127%) and striatum (+150%). VAD induced anatomic and metabolic changes comparable to those associated with neurodegenerative disorders. By wk 7 of deprivation, the slowing in cerebral growth that correlated with the retinol level could be considered as a predictive marker of brain disorders, confirmed by metabolic data from VAD rats after 14wk.

Published
2009

28. Fly stage trypanosomes recycle glucose catabolites and TCA cycle intermediates to stimulate growth in near physiological conditions

Author

Villafraz, Oriana, primary, Biran, Marc, additional, Pineda, Erika, additional, Plazolles, Nicolas, additional, Cahoreau, Edern, additional, Souza, Rodolpho Ornitz Oliveira, additional, Thonnus, Magali, additional, Allmann, Stefan, additional, Tetaud, Emmanuel, additional, Rivière, Loïc, additional, Silber, Ariel M., additional, Barrett, Michael P., additional, Zíková, Alena, additional, Boshart, Michael, additional, Portais, Jean-Charles, additional, and Bringaud, Frédéric, additional

Published
2020
Full Text
View/download PDF

29. Metabolic selection of a homologous recombination mediated loss of glycosomal fumarate reductase inTrypanosoma brucei

Author

Wargnies, Marion, primary, Plazolles, Nicolas, additional, Schenk, Robin, additional, Villafraz, Oriana, additional, Dupuy, Jean-William, additional, Biran, Marc, additional, Bachmaier, Sabine, additional, Baudouin, Hélène, additional, Clayton, Christine, additional, Boshart, Michael, additional, and Bringaud, Frédéric, additional

Published
2020
Full Text
View/download PDF

35. Gluconeogenesis is essential for trypanosome development in the tsetse fly vector

Author

Wargnies, Marion, Bertiaux, Eloise, Cahoreau, Edern, Ziebart, Nicole, Crouzols, Aline, Morand, Pauline, Biran, Marc, Allmann, Stefan, Hubert, Jane, Villafraz, Oriana, Millerioux, Yoann, Plazolles, Nicolas, Asencio, Corinne, Rivière, Loïc, Rotureau, Brice, Boshart, Michael, Portais, Jean-Charles, Bringaud, Frédéric, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), MetaToul FluxoMet (TBI-MetaToul), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ludwig-Maximilians-Universität München (LMU), The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. FB's and BR's group were funded by the Agence Nationale de la Recherche (ANR) through GLYCONOV (grant number ANR-15-CE15-0025-01) of the ANR-BLANC-2015 call. FB's group was supported by the Centre National de la Recherche Scientifique (CNRS), the Université de Bordeaux, the ANR through the grants ACETOTRYP (grant number ANR-2010-BLAN-1319-02) of the ANR-BLANC-2010 call, the Laboratoire d’Excellence (LabEx) ParaFrap ANR-11-LABX-0024 and the ParaMet PhD programme of Marie Curie Initial Training Network. BR’s group was supported by the Institut Pasteur, the Institut National de la Santé et de la Recherche Médicale (INSERM). EB is funded by a doctoral fellowship from French National Ministry for Research and Technology (Doctoral School CDV515). MB was funded by the University of Munich and MB and FB were supported by a research cooperation grant of the Franco-Bavarian University Cooperation Center (BFHZ/CCUFB)., ANR-15-CE15-0025,GLYCONOV,Voies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomes(2015), ANR-10-BLAN-1319,ACETOTRYP,Metabolisme de l'acetyl-CoA et de l'acetate chez les trypanosomes: identification de nouvelles voies métaboliques spécifiques aux parasites(2010), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Résonance magnétique des systèmes biologiques (RMSB), Biologie cellulaire des Trypanosomes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Rotureau, Brice, Voies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomes - - GLYCONOV2015 - ANR-15-CE15-0025 - AAPG2015 - VALID, BLANC - Metabolisme de l'acetyl-CoA et de l'acetate chez les trypanosomes: identification de nouvelles voies métaboliques spécifiques aux parasites - - ACETOTRYP2010 - ANR-10-BLAN-1319 - BLANC - VALID, and Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID

Subjects
Glycerol, gène codant, Disease Vectors, Biochemistry, Salivary Glands, Glucose Metabolism, Medicine and Health Sciences, Biology (General), Amino Acids, Protozoans, surexpression, Organic Compounds, Microbiology and Parasitology, Monosaccharides, Monomers, Eukaryota, Microbiologie et Parasitologie, Chemistry, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, protéine, Physical Sciences, Carbohydrate Metabolism, Anatomy, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, Trypanosoma, Tsetse Flies, Proline, QH301-705.5, Trypanosoma brucei brucei, Carbohydrates, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Phosphates, Exocrine Glands, Parasitic Diseases, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, gluconeogénèse, Organic Chemistry, Gluconeogenesis, Organisms, Chemical Compounds, Biology and Life Sciences, Proteins, Cyclic Amino Acids, RC581-607, mouche tsé tsé, Polymer Chemistry, Parasitic Protozoans, enzyme, Trypanosomiasis, African, Metabolism, Glucose, Immunologic diseases. Allergy, Digestive System, trypanosoma brucei
Abstract

In the glucose-free environment that is the midgut of the tsetse fly vector, the procyclic form of Trypanosoma brucei primarily uses proline to feed its central carbon and energy metabolism. In these conditions, the parasite needs to produce glucose 6-phosphate (G6P) through gluconeogenesis from metabolism of non-glycolytic carbon source(s). We showed here that two phosphoenolpyruvate-producing enzymes, PEP carboxykinase (PEPCK) and pyruvate phosphate dikinase (PPDK) have a redundant function for the essential gluconeogenesis from proline. Indeed, incorporation of 13C-enriched proline into G6P was abolished in the PEPCK/PPDK null double mutant (Δppdk/Δpepck), but not in the single Δppdk and Δpepck mutant cell lines. The procyclic trypanosome also uses the glycerol conversion pathway to feed gluconeogenesis, since the death of the Δppdk/Δpepck double null mutant in glucose-free conditions is only observed after RNAi-mediated down-regulation of the expression of the glycerol kinase, the first enzyme of the glycerol conversion pathways. Deletion of the gene encoding fructose-1,6-bisphosphatase (Δfbpase), a key gluconeogenic enzyme irreversibly producing fructose 6-phosphate from fructose 1,6-bisphosphate, considerably reduced, but not abolished, incorporation of 13C-enriched proline into G6P. In addition, the Δfbpase cell line is viable in glucose-free conditions, suggesting that an alternative pathway can be used for G6P production in vitro. However, FBPase is essential in vivo, as shown by the incapacity of the Δfbpase null mutant to colonise the fly vector salivary glands, while the parental phenotype is restored in the Δfbpase rescued cell line re-expressing FBPase. The essential role of FBPase for the development of T. brucei in the tsetse was confirmed by taking advantage of an in vitro differentiation assay based on the RNA-binding protein 6 over-expression, in which the procyclic forms differentiate into epimastigote forms but not into mammalian-infective metacyclic parasites. In total, morphology, immunofluorescence and cytometry analyses showed that the differentiation of the epimastigote stages into the metacyclic forms is abolished in the Δfbpase mutant., Author summary Trypanosoma brucei, the parasite responsible for sleeping sickness in humans, is transmitted by the tsetse fly that primarily uses amino acids for its energy production. In the glucose-free environment encountered between the insect blood meals, T. brucei needs to produce through gluconeogenesis glucose 6-phosphate, a key precursor for several essential metabolic pathways. We have shown here that two key gluconeogenic steps, which produce phosphoenolpyruvate and fructose 6-phosphate, respectively, are performed by redundant enzymes (PPDK and PEPCK for phosphoenolpyruvate production; FBPase and a yet unknown enzyme for fructose 6-phosphate production), which highlights the importance of this metabolic pathway for the insect stages of the parasite. Interestingly, deletion of the parasite FBPase gene abolished both the colonisation of the insect salivary glands and the in vitro differentiation of the epimastigote forms into the mammalian infective form of the parasite. Altogether, these data demonstrate for the first time that gluconeogenesis is essential for development of T. brucei in its insect vector and that early development stages of the parasite present in the tsetse midgut are not affected by the absence of FBPase, probably by developing an alternative yet unknown approach to produce fructose 6-phosphate.

Published
2018
Full Text
View/download PDF

36. De novo biosynthesis of sterols and fatty acids in the Trypanosoma brucei procyclic form: Carbon source preferences and metabolic flux redistributions

Author

Millerioux, Yoann, Mazet, Muriel, Bouyssou, Guillaume, Allmann, Stefan, Kiema, Tiila-Riikka, Bertiaux, Eloise, Fouillen, Laetitia, Thapa, Chandan, Biran, Marc, Plazolles, Nicolas, Dittrich-Domergue, Franziska, Crouzols, Aline, Wierenga, Rik, Rotureau, Brice, MOREAU, Patrick, Bringaud, Frédéric, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biogenèse membranaire (LBM), University of Oulu, Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This research was supported by the Centre National de la Recherche Scientifique (CNRS), the Université de Bordeaux, the Agence Nationale de la Recherche (ANR) through grants ACETOTRYP (grant number ANR-2010-BLAN-1319-02) of the ANR-BLANC-2010 call and GLYCONOV (grant number ANR-15-CE15-0025-01) of the 'Générique' 2015 call, the Laboratoire d’Excellence (LabEx) ParaFrap (grant number ANR-11-LABX-0024), the Institut Pasteur and by the European Commission FP7 Marie Curie Initial Training Network 'ParaMet' (grant number 290080). EB was funded by a doctoral fellowship from French National Ministry for Research and Technology (doctoral school CDV515)., ANR-10-BLAN-1319,ACETOTRYP,Metabolisme de l'acetyl-CoA et de l'acetate chez les trypanosomes: identification de nouvelles voies métaboliques spécifiques aux parasites(2010), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: 290080,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,PARAMET(2012), Résonance magnétique des systèmes biologiques (RMSB), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Biologie cellulaire des Trypanosomes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Rotureau, Brice, BLANC - Metabolisme de l'acetyl-CoA et de l'acetate chez les trypanosomes: identification de nouvelles voies métaboliques spécifiques aux parasites - - ACETOTRYP2010 - ANR-10-BLAN-1319 - BLANC - VALID, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, and A systematic analysis of parasite metabolism - from metabolism to intervention - PARAMET - - EC:FP7:PEOPLE2012-06-01 - 2016-05-31 - 290080 - VALID

Subjects
Threonine, [SDV]Life Sciences [q-bio], blood-sream forms, Acetates, Biochemistry, molecular characterization, Gene Knockout Techniques, dependent enzyme, Glucose Metabolism, proline metabolism, MESH: Animals, Amino Acids, MESH: Threonine, lcsh:QH301-705.5, MESH: Gene Knockout Techniques, Protozoans, MESH: Tsetse Flies, Organic Compounds, Fatty Acids, Monosaccharides, Eukaryota, cell-cycle, acetyl-coa, energy-metabolism, lipbiosyntesis, leishmania-mexicana, succinate coa-transferase, MESH: Mevalonic Acid, Lipids, MESH: Gene Expression Regulation, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Fatty Acids, [SDV] Life Sciences [q-bio], MESH: Glucose, Sterols, Chemistry, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Physical Sciences, Carbohydrate Metabolism, MESH: Acetates, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, lcsh:Immunologic diseases. Allergy, Trypanosoma, Proline, Tsetse Flies, Trypanosoma brucei brucei, Carbohydrates, Mevalonic Acid, MESH: Carbon, MESH: Insect Vectors, Biosynthesis, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, MESH: Alcohol Oxidoreductases, Acetyl Coenzyme A, Acetyltransferases, Leucine, Hydroxyl Amino Acids, MESH: Acyl Coenzyme A, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Proline, Organic Chemistry, Organisms, Chemical Compounds, Biology and Life Sciences, Proteins, MESH: Trypanosoma brucei brucei, MESH: Acetyltransferases, Carbon, Parasitic Protozoans, Insect Vectors, Alcohol Oxidoreductases, Glucose, Metabolism, MESH: Leucine, Gene Expression Regulation, Aliphatic Amino Acids, lcsh:Biology (General), MESH: Sterols, Acyl Coenzyme A, lcsh:RC581-607, MESH: Acetyl Coenzyme A
Abstract

De novo biosynthesis of lipids is essential for Trypanosoma brucei, a protist responsible for the sleeping sickness. Here, we demonstrate that the ketogenic carbon sources, threonine, acetate and glucose, are precursors for both fatty acid and sterol synthesis, while leucine only contributes to sterol production in the tsetse fly midgut stage of the parasite. Degradation of these carbon sources into lipids was investigated using a combination of reverse genetics and analysis of radio-labelled precursors incorporation into lipids. For instance, (i) deletion of the gene encoding isovaleryl-CoA dehydrogenase, involved in the leucine degradation pathway, abolished leucine incorporation into sterols, and (ii) RNAi-mediated down-regulation of the SCP2-thiolase gene expression abolished incorporation of the three ketogenic carbon sources into sterols. The SCP2-thiolase is part of a unidirectional two-step bridge between the fatty acid precursor, acetyl-CoA, and the precursor of the mevalonate pathway leading to sterol biosynthesis, 3-hydroxy-3-methylglutaryl-CoA. Metabolic flux through this bridge is increased either in the isovaleryl-CoA dehydrogenase null mutant or when the degradation of the ketogenic carbon sources is affected. We also observed a preference for fatty acids synthesis from ketogenic carbon sources, since blocking acetyl-CoA production from both glucose and threonine abolished acetate incorporation into sterols, while incorporation of acetate into fatty acids was increased. Interestingly, the growth of the isovaleryl-CoA dehydrogenase null mutant, but not that of the parental cells, is interrupted in the absence of ketogenic carbon sources, including lipids, which demonstrates the essential role of the mevalonate pathway. We concluded that procyclic trypanosomes have a strong preference for fatty acid versus sterol biosynthesis from ketogenic carbon sources, and as a consequence, that leucine is likely to be the main source, if not the only one, used by trypanosomes in the infected insect vector digestive tract to feed the mevalonate pathway., Author summary In this study, we have (i) determined the carbon sources used by the Trypanosoma brucei procyclic insect form to feed the essential lipid biosynthetic pathways, (ii) further characterized the metabolic pathways leading to their degradation into acetyl-CoA (fatty acid precursor) and 3-hydroxy-3-methylglutaryl-CoA (sterol precursor) and (iii) showed that reduction of the ketogenic carbon sources degradation, favors their incorporation into fatty acids, instead of sterols. This fatty acid preference is compensated by an increase of leucine incorporation into sterols, which highlights the parasite adaptation capacity regarding carbon source availability by modulating the metabolic flux between branches within the network. This metabolic flexibility is particularly relevant for the insect stages of trypanosomes that evolve in the midgut and the salivary glands of their blood-feeding insect vector. One may also consider that, the metabolic flow redistribution towards the mevalonate pathway (sterol production) described in vitro also occurs in vivo, depending on the carbon source composition of the tsetse fly micro-environment, which may considerably vary along the digestive tract and depending on the fly feeding status, as well as in the other infected fly organs.

Published
2018
Full Text
View/download PDF

37. “Metabolic contest”, a new way to control carbon source preference

Author

Allmann, Stefan, primary, Wargnies, Marion, additional, Cahoreau, Edern, additional, Biran, Marc, additional, Plazolles, Nicolas, additional, Morand, Pauline, additional, Pineda, Erika, additional, Kulyk, Hanna, additional, Asencio, Corinne, additional, Villafraz, Oriana, additional, Rivière, Loïc, additional, Tétaud, Emmanuel, additional, Rotureau, Brice, additional, Mourier, Arnaud, additional, Portais, Jean-Charles, additional, and Bringaud, Frédéric, additional

Published
2019
Full Text
View/download PDF

42. Proline metabolism is essential for trypanosoma brucei brucei survival in the tsetse vector

Author

Mantilla, Brian S., Marchese, Letícia, Casas-Sánchez, Aitor, Dyer, Naomi A., Ejeh, Nicholas, Biran, Marc, Bringaud, Frédéric, Lehane, Michael J., Acosta-Serrano, Alvaro, Silber, Ariel M., Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), and Liverpool School of Tropical Medicine (LSTM)

Subjects
Magnetic Resonance Spectroscopy, Cell Separation, Biochemistry, Glucose Metabolism, Medicine and Health Sciences, Amino Acids, Biology (General), Energy-Producing Organelles, ComputingMilieux_MISCELLANEOUS, Alanine, Organic Compounds, Monosaccharides, Neurochemistry, Neurotransmitters, Flow Cytometry, Adaptation, Physiological, Mitochondria, Chemistry, Gene Knockdown Techniques, Physical Sciences, Carbohydrate Metabolism, Cellular Structures and Organelles, Glutamate, Research Article, Proline, Tsetse Flies, QH301-705.5, Blotting, Western, Trypanosoma brucei brucei, Carbohydrates, Bioenergetics, Host-Parasite Interactions, Trypanosomiasis, Parasitic Diseases, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Organic Chemistry, fungi, Chemical Compounds, Biology and Life Sciences, Proteins, Cyclic Amino Acids, Cell Biology, RC581-607, Insect Vectors, Amino Acid Metabolism, Metabolism, Glucose, Aliphatic Amino Acids, Microscopy, Fluorescence, Immunologic diseases. Allergy, Neuroscience
Abstract

Adaptation to different nutritional environments is essential for life cycle completion by all Trypanosoma brucei sub-species. In the tsetse fly vector, L-proline is among the most abundant amino acids and is mainly used by the fly for lactation and to fuel flight muscle. The procyclic (insect) stage of T. b. brucei uses L-proline as its main carbon source, relying on an efficient catabolic pathway to convert it to glutamate, and then to succinate, acetate and alanine as the main secreted end products. Here we investigated the essentiality of an undisrupted proline catabolic pathway in T. b. brucei by studying mitochondrial Δ1-pyrroline-5-carboxylate dehydrogenase (TbP5CDH), which catalyzes the irreversible conversion of gamma-glutamate semialdehyde (γGS) into L-glutamate and NADH. In addition, we provided evidence for the absence of a functional proline biosynthetic pathway. TbP5CDH expression is developmentally regulated in the insect stages of the parasite, but absent in bloodstream forms grown in vitro. RNAi down-regulation of TbP5CDH severely affected the growth of procyclic trypanosomes in vitro in the absence of glucose, and altered the metabolic flux when proline was the sole carbon source. Furthermore, TbP5CDH knocked-down cells exhibited alterations in the mitochondrial inner membrane potential (ΔΨm), respiratory control ratio and ATP production. Also, changes in the proline-glutamate oxidative capacity slightly affected the surface expression of the major surface glycoprotein EP-procyclin. In the tsetse, TbP5CDH knocked-down cells were impaired and thus unable to colonize the fly’s midgut, probably due to the lack of glucose between bloodmeals. Altogether, our data show that the regulated expression of the proline metabolism pathway in T. b. brucei allows this parasite to adapt to the nutritional environment of the tsetse midgut., Author Summary Bloodsucking insects play a major role in the transmission of pathogens that cause major tropical diseases. Their capacity to transmit these diseases is directly associated with the availability and turnover of energy sources. Proline is the main readily-mobilizable fuel of the tsetse fly, which is the vector of sub-species of Trypanosoma brucei parasites that cause human sleeping sickness and are partly responsible for animal trypanosomiasis (Nagana disease) in sub-Saharan Africa. Once trypanosomes are ingested from an infected host by the tsetse, the parasites encounter an environment that is poor in glucose (as it is rapidly metabolized by the fly) but rich in proline, which then becomes the main carbon source once the parasite differentiates into the first insect (procyclic) stage. In this work, we provide evidence on the essentiality of T. b. brucei proline catabolism for procyclic survival within the tsetse’s digestive tract, as this organism is unable to synthesize this amino acid and strictly depends on the proline provided by the fly. We also show that parasites deficient in TbP5CDH, a mitochondrial enzyme involved in the proline degradative pathway, failed to proliferate in vitro, showed a diminished respiratory capacity, and showed compromised maintenance of energy levels and metabolic flux when proline was offered as the main carbon source. Thus, the integrity of the trypanosome proline degradation pathway is needed to maintain essential functions related to parasite bioenergetics, replication and infectivity within the insect host. Our observations answer a long-standing question on the role of parasite proline metabolism in tsetse-trypanosome interplay.

Published
2017
Full Text
View/download PDF

43. Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: Analysis of metabolic adaptations on glycerol-rich conditions

Author

Pineda, Erika, primary, Thonnus, Magali, additional, Mazet, Muriel, additional, Mourier, Arnaud, additional, Cahoreau, Edern, additional, Kulyk, Hanna, additional, Dupuy, Jean-William, additional, Biran, Marc, additional, Masante, Cyril, additional, Allmann, Stefan, additional, Rivière, Loïc, additional, Rotureau, Brice, additional, Portais, Jean-Charles, additional, and Bringaud, Frédéric, additional

Published
2018
Full Text
View/download PDF

44. Mitochondrial pyruvate carrier in T rypanosoma brucei

Author

Štáfková, Jitka, Mach, Jan, Biran, Marc, Verner, Zdeněk, Bringaud, Frédéric, Tachezy, Jan, Department of Parasitology, Faculty of Science, Charles University in Prague, Faculty of Science, Charles University in Prague, Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Department of Parasitology, Faculty of Science, and Charles University [Prague] (CU)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016
Full Text
View/download PDF

45. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose

Author

Creek, Darren J., Mazet, Muriel, Achcar, Fiona, Anderson, Jana, Kim, Dong-Hyun, Kamour, Ruwida, Morand, Pauline, Millerioux, Yoann, Biran, Marc, Kerkhoven, Eduard J., Chokkathukalam, Achuthanunni, Weidt, Stefan K., Burgess, Karl E.V., Breitling, Rainer, Watson, David G., Bringaud, Frédéric, Barrett, Michael, Monash University [Melbourne], Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Chalmers University of Technology [Göteborg], University of Glasgow, University of Manchester [Manchester], University of Strathclyde [Glasgow], Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), University of Strathclyde, and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Glycerol, QH301-705.5, Trypanosoma brucei brucei, Immunology, Succinic Acid, Microbiology, RS, Pentose Phosphate Pathway, Virology, Genetics, Animals, Metabolomics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Biology (General), Molecular Biology, Cells, Cultured, RC581-607, Glucose, Parasitology, Immunologic diseases. Allergy, Oxidation-Reduction, Metabolic Networks and Pathways, Research Article
Abstract

Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate., Author Summary In this work we have followed the distribution of carbon derived from glucose in bloodstream form trypanosomes, the causative agent of African trypanosomiasis, revealing it to enter a diverse range of metabolites. The work involved using 13C-labelled glucose and following the fate of the labelled carbon with an LC-MS based metabolomics platform. Beyond glycolysis and the oxidative branch of the pentose phosphate pathway the label entered lipid biosynthesis both through glycerol 3-phosphate and also acetate. Glucose derived carbon also entered nucleotide synthesis through ribose and pyrimidine synthesis through oxaloacetate-derived aspartate. Appreciable quantities of the carboxylic acids succinate and malate were identified, although labelling patterns indicate they are not TCA cycle derived. Amino sugars and sugar nucleotides were also labelled as was inositol used in protein modification but not in inositol phospholipid headgroup production. We confirm active and essential oxaloacetate production in bloodstream form trypanosomes and show that phosphoenolpyruvate carboxykinase is essential to these parasites using RNA interference. The amount of glucose entering these metabolites is minor compared to the quantity that enters pyruvate excreted from the cell, but the observation that enzymes contributing to the metabolism of glucose beyond glycolysis can be essential offers potential new targets for chemotherapy against trypanosomiasis.

Published
2015
Full Text
View/download PDF

47. Revisiting the Central Metabolism of the Bloodstream Forms of Trypanosoma brucei: Production of Acetate in the Mitochondrion Is Essential for Parasite Viability

Author

Mazet, Muriel, primary, Morand, Pauline, additional, Biran, Marc, additional, Bouyssou, Guillaume, additional, Courtois, Pierrette, additional, Daulouède, Sylvie, additional, Millerioux, Yoann, additional, Franconi, Jean-Michel, additional, Vincendeau, Philippe, additional, Moreau, Patrick, additional, and Bringaud, Frédéric, additional

Published
2013
Full Text
View/download PDF

48. Mitochondrial energetics is impairedin vivoin aged skeletal muscle

Author

Gouspillou, Gilles, primary, Bourdel-Marchasson, Isabelle, additional, Rouland, Richard, additional, Calmettes, Guillaume, additional, Biran, Marc, additional, Deschodt-Arsac, Véronique, additional, Miraux, Sylvain, additional, Thiaudiere, Eric, additional, Pasdois, Philippe, additional, Detaille, Dominique, additional, Franconi, Jean-Michel, additional, Babot, Marion, additional, Trézéguet, Véronique, additional, Arsac, Laurent, additional, and Diolez, Philippe, additional

Published
2013
Full Text
View/download PDF

49. The threonine degradation pathway of theTrypanosoma bruceiprocyclic form: the main carbon source for lipid biosynthesis is under metabolic control

Author

Millerioux, Yoann, primary, Ebikeme, Charles, additional, Biran, Marc, additional, Morand, Pauline, additional, Bouyssou, Guillaume, additional, Vincent, Isabel M., additional, Mazet, Muriel, additional, Riviere, Loïc, additional, Franconi, Jean-Michel, additional, Burchmore, Richard J. S., additional, Moreau, Patrick, additional, Barrett, Michael P., additional, and Bringaud, Frédéric, additional

Published
2013
Full Text
View/download PDF

50. MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis

Author

Jacobin-Valat, Marie-Josée, primary, Deramchia, Kamel, additional, Mornet, Stéphane, additional, Hagemeyer, Christoph E., additional, Bonetto, Stéphane, additional, Robert, Rémy, additional, Biran, Marc, additional, Massot, Philippe, additional, Miraux, Sylvain, additional, Sanchez, Stéphane, additional, Bouzier-Sore, Anne-Karine, additional, Franconi, Jean-Michel, additional, Duguet, Etienne, additional, and Clofent-Sanchez, Gisèle, additional

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results