Z. Hao, I. Kasumba, A. , and S. , Proventriculus (cardia) plays a crucial role in immunity in tsetse fly (Diptera: Glossinidiae), Insect. Biochem. Mol. Biol, vol.33, pp.1155-1164, 2003.

S. Müller, Redox and antioxidant systems of the malaria parasite Plasmodium falciparum, Mol. Microbiol, vol.53, pp.1291-1305, 2004.

S. E. Akerman and S. Müller, Peroxiredoxin-linked detoxification of hydroperoxides in Toxoplasma gondii, J. Biol. Chem, vol.280, pp.564-570, 2005.

A. Boveris, H. Sies, E. E. Martino, R. Docampo, J. F. Turrens et al., Deficient metabolic utilization of hydrogen peroxide in Trypanosoma cruzi, Biochem. J, vol.188, pp.643-648, 1980.

S. He, A. Dayton, P. Kuppusamy, K. A. Werbovetz, and M. E. Drew, Induction of oxidative stress in Trypanosoma brucei by the antitrypanosomal dihydroquinoline OSU-40, Antimicrob. Agents Chemother, vol.56, pp.2428-2434, 2012.

A. Lüscher, H. P. De-koning, and P. Mäser, Chemotherapeutic strategies against Trypanosoma brucei: drug targets vs. drug targeting, Curr. Pharm. Des, vol.13, pp.555-567, 2007.

I. B. Müller, R. Das-gupta, K. Lüersen, C. Wrenger, and R. D. Walter, Assessing the polyamine metabolism of Plasmodium falciparum as chemotherapeutic target, Mol. Biochem. Parasitol, vol.160, pp.1-7, 2008.

L. M. Birkholtz, M. Williams, J. Niemand, A. I. Louw, L. Persson et al., Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities, Biochem. J, vol.438, pp.229-244, 2011.

R. L. Krauth-siegel and M. A. Comini, Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism, Biochim. Biophys. Acta, vol.1780, pp.1236-1248, 2008.

A. H. Fairlamb, P. Blackburn, P. Ulrich, B. T. Chait, and A. Cerami, Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids, Science, vol.227, pp.1485-1487, 1985.

B. A. Arrick, O. W. Griffith, and A. Cerami, Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanosomiasis, J. Exp. Med, vol.153, pp.720-725, 1981.

S. Krieger, W. Schwarz, M. R. Ariyanayagam, A. H. Fairlamb, R. L. Krauthsiegel et al., Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress, Mol. Microbiol, vol.35, pp.542-552, 2000.

T. T. Huynh, V. T. Huynh, M. A. Harmon, and M. A. Phillips, Gene knockdown of ?-glutamylcysteine synthetase by RNAi in the parasitic protozoa Trypanosoma brucei demonstrates that it is an essential enzyme, J. Biol. Chem, vol.278, pp.39794-39800, 2003.

M. A. Comini, R. L. Krauth-siegel, and L. Flohé, Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes, Biochem. J, vol.402, pp.43-49, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00478658

M. P. Barrett, The pentose phosphate pathway and parasitic protozoa, Parasitol. Today, vol.13, pp.11-16, 1997.

N. Heise and F. R. Opperdoes, Purification, localisation and characterisation of glucose-6-phosphate dehydrogenase of Trypanosoma brucei, Mol. Biochem. Parasitol, vol.99, pp.21-32, 1999.

F. Duffieux, J. Van-roy, P. A. Michels, and F. R. Opperdoes, Molecular characterization of the first two enzymes of the pentose-phosphate pathway of Trypanosoma brucei: glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase, J. Biol. Chem, vol.275, pp.27559-27565, 2000.

M. Igoillo-esteve, D. Maugeri, A. L. Stern, P. Beluardi, and J. J. Cazzulo, The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease, An. Acad. Bras. Cienc, vol.79, pp.649-663, 2007.

S. H. Lee, J. L. Stephens, and P. T. Englund, A fatty-acid synthesis mechanism specialized for parasitism, Nat. Rev. Microbiol, vol.5, pp.287-297, 2007.
DOI : 10.1038/nrmicro1617

M. P. Barrett and I. H. Gilbert, Perspectives for new drugs against trypanosomiasis and leishmaniasis, Curr. Top. Med. Chem, vol.2, pp.471-482, 2002.
DOI : 10.2174/1568026024607427

A. T. Cordeiro, O. H. Thiemann, and P. A. Michels, Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites, Bioorg. Med. Chem, vol.17, pp.2483-2489, 2009.

A. E. Leroux, D. A. Maugeri, F. R. Opperdoes, J. J. Cazzulo, and C. Nowicki, Comparative studies on the biochemical properties of the malic enzymes from Trypanosoma cruzi and Trypanosoma brucei, FEMS Microbiol. Lett, vol.314, pp.25-33, 2011.

R. Brun and S. , Cultivation and in vitro cloning or procyclic culture forms of Trypanosoma brucei in a semi-defined medium, Acta Trop, vol.36, pp.289-292, 1979.

L. Azema, S. Claustre, I. Alric, C. Blonski, M. Willson et al., Interaction of substituted hexose analogues with the Trypanosoma brucei hexose transporter, Biochem. Pharmacol, vol.67, pp.459-467, 2004.

H. Ngô, C. Tschudi, K. Gull, and E. Ullu, Double-stranded RNA induces mRNA degradation in Trypanosoma brucei, Proc. Natl. Acad. Sci. U.S.A, vol.95, pp.14687-14692, 1998.

F. Bringaud, D. R. Robinson, S. Barradeau, N. Biteau, D. Baltz et al., Characterization and disruption of a new Trypanosoma brucei repetitive flagellum protein, using double-stranded RNA inhibition, Mol. Biochem. Parasitol, vol.111, pp.283-297, 2000.

E. Wirtz, S. Leal, C. Ochatt, and G. A. Cross, A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei, Mol. Biochem. Parasitol, vol.99, pp.89-101, 1999.

V. Coustou, M. Biran, M. Breton, F. Guegan, L. Rivière et al., Glucoseinduced remodeling of intermediary and energy metabolism in procyclic Trypanosoma brucei, J. Biol. Chem, vol.283, pp.16342-16354, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00318595

L. Rivière, S. W. Van-weelden, P. Glass, P. Vegh, V. Coustou et al., Acetyl:succinate CoA-transferase in procyclic Trypanosoma brucei. Gene identification and role in carbohydrate metabolism, J. Biol. Chem, vol.279, pp.45337-45346, 2004.

R. A. Klein, D. J. Linstead, and M. V. Wheeler, Carbon dioxide fixation in trypanosomatids, Parasitology, vol.71, pp.93-107, 1975.

E. Harlow and D. Lane, Antibodies: A Laboratory Manual, pp.471-502, 1988.

J. Sambrook, E. F. Fritsch, and T. Maniatis, Molecular Cloning: A Laboratory Manual, 1989.

V. Coustou, M. Biran, S. Besteiro, L. Rivière, T. Baltz et al., Fumarate is an essential intermediary metabolite produced by the procyclic Trypanosoma brucei, J. Biol. Chem, vol.281, pp.26832-26846, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00215929

E. Tetaud, C. Giroud, A. R. Prescott, D. W. Parkin, D. Baltz et al., Molecular characterisation of mitochondrial and cytosolic trypanothione-dependent tryparedoxin peroxidases in Trypanosoma brucei, Mol. Biochem. Parasitol, vol.116, pp.171-183, 2001.

L. Kohl, T. Sherwin, and K. Gull, Assembly of the paraflagellar rod and the flagellum attachment zone complex during the Trypanosoma brucei cell cycle, J. Eukaryot. Microbiol, vol.46, pp.105-109, 1999.

S. A. Ahmed, R. M. Gogal, and J. E. Walsh, A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: an alternative to, 1994.

, H]thymidine incorporation assay

, J. Immunol. Methods, vol.170, pp.211-224

B. Räz, M. Iten, Y. Grether-bühler, R. Kaminsky, and R. Brun, The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro, Acta Trop, vol.68, pp.139-147, 1997.

C. Ebikeme, J. Hubert, M. Biran, G. Gouspillou, P. Morand et al., Ablation of succinate production from glucose metabolism in the procyclic trypanosomes induces metabolic switches to the glycerol 3-phosphate/dihydroxyacetone phosphate shuttle and to proline metabolism, J. Biol. Chem, vol.285, pp.32312-32324, 2010.

C. J. Bolten, P. Kiefer, F. Letisse, J. C. Portais, and C. Wittmann, Sampling for metabolome analysis of microorganisms, Anal. Chem, vol.79, pp.3843-3849, 2007.
URL : https://hal.archives-ouvertes.fr/hal-02183185

P. Kiefer, C. Nicolas, F. Letisse, and J. C. Portais, Determination of carbon labeling distribution of intracellular metabolites from single fragment ions by ion chromatography tandem mass spectrometry, 2007.
URL : https://hal.archives-ouvertes.fr/hal-02183207

, Biochem, vol.360, pp.182-188

P. Millard, F. Letisse, S. Sokol, and J. C. Portais, IsoCor: correcting MS data in isotope labeling experiments, Bioinformatics, vol.28, pp.1294-1296, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01268343

J. J. Cannata, A. C. Frasch, M. A. Cataldi-de-flombaum, E. L. Segura, and J. J. Cazzulo, Two forms of 'malic' enzyme with different regulatory properties in Trypanosoma cruzi, Biochem. J, vol.184, pp.409-419, 1979.

E. Orellano and J. J. Cazzulo, Purification and regulatory properties of the NADP-linked malic enzyme for Crithidia fasciculata, Mol. Biochem. Parasitol, vol.3, pp.1-11, 1981.

S. Gupta, A. T. Cordeiro, and P. A. Michels, Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids, Mol. Biochem. Parasitol, vol.176, pp.112-115, 2011.

A. K. Ingram, G. A. Cross, and D. Horn, Genetic manipulation indicates that ARD1 is an essential N ? -acetyltransferase in Trypanosoma brucei, Mol. Biochem. Parasitol, vol.111, pp.309-317, 2000.

A. Mannaert, T. Downing, H. Imamura, and J. C. Dujardin, Adaptive mechanisms in pathogens: universal aneuploidy in Leishmania, Trends Parasitol, vol.28, pp.370-376, 2012.

C. N. Cronín, D. P. Nolan, and H. P. Voorheis, The enzymes of the classical pentose phosphate pathway display differential activities in procyclic and bloodstream forms of Trypanosoma brucei, FEBS Lett, vol.244, pp.26-30, 1989.

D. J. Creek, A. Chokkathukalam, A. Jankevics, K. E. Burgess, R. Breitling et al., Stable isotope-assisted metabolomics for network-wide metabolic pathway elucidation, Anal. Chem, vol.84, pp.8442-8447, 2012.

K. Pantopoulos, S. Mueller, A. Atzberger, W. Ansorge, W. Stremmel et al., Differences in the regulation of iron regulatory protein-1 (IRP-1) by extra-and intracellular oxidative stress, J. Biol. Chem, vol.272, pp.9802-9808, 1997.

A. Sureda, U. Hebling, A. Pons, and S. Mueller, Extracellular H 2 O 2 and not superoxide determines the compartment-specific activation of transferrin receptor by iron regulatory protein 1, Free Radic. Res, vol.39, pp.817-824, 2005.

S. Mueller, Sensitive and nonenzymatic measurement of hydrogen peroxide in biological systems. Free Radic, Biol. Med, vol.29, pp.410-415, 2000.

P. A. Michels, F. Bringaud, M. Herman, and V. Hannaert, Metabolic functions of glycosomes in trypanosomatids, Biochim. Biophys. Acta, vol.1763, pp.1463-1477, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00215923

N. Lamour, L. Rivière, V. Coustou, G. H. Coombs, M. P. Barrett et al., Proline metabolism in procyclic Trypanosoma brucei is down-regulated in the presence of glucose, J. Biol. Chem, vol.280, pp.11902-11910, 2005.

S. W. Van-weelden, B. Fast, A. Vogt, P. Van-der-meer, J. Saas et al., Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation, J. Biol. Chem, vol.278, pp.12854-12863, 2003.

E. Bursell and R. G. Downer, The role of proline in energy metabolism, Energy Metabolism in Insects, pp.135-154, 1981.

M. Berriman, E. Ghedin, C. Hertz-fowler, G. Blandin, H. Renauld et al., The genome of the African trypanosome Trypanosoma brucei, vol.309, pp.416-422, 2005.

V. Hannaert, E. Saavedra, F. Duffieux, J. P. Szikora, D. J. Rigden et al., Plant-like traits associated with metabolism of Trypanosoma parasites, Proc. Natl. Acad. Sci. U.S.A, vol.100, pp.1067-1071, 2003.

V. Coustou, S. Besteiro, L. Rivière, M. Biran, N. Biteau et al., A mitochondrial NADHdependent fumarate reductase involved in the production of succinate excreted by procyclic Trypanosoma brucei, J. Biol. Chem, vol.280, pp.16559-16570, 2005.

A. Ghozlane, F. Bringaud, H. Soueidan, I. Dutour, F. Jourdan et al., Flux analysis of the Trypanosoma brucei glycolysis based on a multiobjective-criteria bioinformatic approach, Adv. Bioinformatics, vol.2012, p.159423, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00723179

F. Bringaud, D. Baltz, and T. Baltz, Functional and molecular characterization of a glycosomal PP i -dependent enzyme in trypanosomatids: pyruvate, phosphate dikinase, Proc. Natl. Acad. Sci. U.S.A, vol.95, pp.7963-7968, 1998.

H. Suga, F. Matsuda, T. Hasunuma, J. Ishii, and A. Kondo, Implementation of a transhydrogenase-like shunt to counter redox imbalance during xylose fermentation in Saccharomyces cerevisiae, Appl. Microbiol. Biotechnol, vol.97, pp.1669-1678, 2013.

T. Naderer, M. A. Ellis, M. F. Sernee, D. P. De-souza, J. Curtis et al., Virulence of Leishmania major in macrophages and mice requires the gluconeogenic enzyme fructose-1,6-bisphosphatase, Proc. Natl. Acad. Sci. U.S.A, vol.103, pp.5502-5507, 2006.

A. Garami and T. Ilg, Disruption of mannose activation in Leishmania mexicana: GDP-mannose pyrophosphorylase is required for virulence, but not for viability, EMBO J, vol.20, pp.3657-3666, 2001.

M. J. Mcconville and T. Naderer, Metabolic pathways required for the intracellular survival of Leishmania, Annu. Rev. Microbiol, vol.65, pp.543-561, 2011.

P. Jiang, W. Du, A. Mancuso, K. E. Wellen, Y. et al., Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence, Nature, vol.493, pp.689-693, 2013.

F. Bringaud, M. P. Barrett, and D. Zilberstein, Multiple roles of proline transport and metabolism in trypanosomatids, Front. Biosci, vol.17, pp.349-374, 2012.

J. Portais,

A. Hubert, M. Brennand, J. Mazet, . Franconi, A. M. Paul et al., Jane Gluconeogenic Flux Relies on Malic Enzyme and the Pentose Phosphate Pathway Fed by Trypanosoma brucei

, Cytosolic NADPH Homeostasis in Glucose-starved Procyclic, vol.288, pp.18494-18505, 2013.

, J. Biol. Chem

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