108 research outputs found
Glycerol suppresses glucose consumption in trypanosomes through metabolic contest
No full textThe file contains all the source data presented in the manuscript:
Allmann S., M. Wargnies, E. Cahoreau, M. Biran, N. Plazolles, P. Morand, E. Pineda, H. Kulyk-Babier, C. Asencio, O. Villafraz, L. Rivière, E. Tetaud, B. Rotureau, A. Mourier, J.-C. Portais, & F. Bringaud (2021) Glycerol suppresses glucose consumption in Trypanosomes through metabolic contest. PLoS Biol
Metabolic aspects of glycosomes in trypanosomatidae - new data and views.
No full textThe energy metabolism of Trypanosomatidae has been the subject of many reviews during the past decade. In recent years, however, new data have led to a more complete picture of trypanosomatid metabolism and a reappraisal of the role of some characteristic organelles in the energy supply of these parasites. For years, the glycosome was thought to be a peroxisome-like organelle that had evolved to allow the parasites to carry out glycolysis at a high rate using a relatively small amount of enzyme. However, the results of recent studies of trypanosomatid glycolysis and the detection of various other pathways and enzymes in the organelle necessitate a modification of this view. Here, Paul Michels, Véronique Hannaert and Frédéric Bringaud review the new data and discuss the possible implications for our view on the role of the glycosome
The genome of the heartworm, Dirofilaria immitis, reveals drug and vaccine targets
No full textThe heartworm Dirofilaria immitis is an important parasite of dogs. Transmitted by mosquitoes in warmer climatic zones, it is spreading across southern Europe and the Americas at an alarming pace. There is no vaccine, and chemotherapy is prone to complications. To learn more about this parasite, we have sequenced the genomes of D. immitis and its endosymbiont Wolbachia. We predict 10,179 protein coding genes in the 84.2 Mb of the nuclear genome, and 823 genes in the 0.9-Mb Wolbachia genome. The D. immitis genome harbors neither DNA transposons nor active retrotransposons, and there is very little genetic variation between two sequenced isolates from Europe and the United States. The differential presence of anabolic pathways such as heme and nucleotide biosynthesis hints at the intricate metabolic interrelationship between the heartworm and Wolbachia. Comparing the proteome of D. immitis with other nematodes and with mammalian hosts, we identify families of potential drug targets, immune modulators, and vaccine candidates. This genome sequence will support the development of new tools against dirofilariasis and aid efforts to combat related human pathogens, the causative agents of lymphatic filariasis and river blindness
Peer Review #1 of "Pollen extracts and constituent sugars increase growth of a trypanosomatid parasite of bumble bees (v0.2)"
No full textPeer Review #1 of "Pollen extracts and constituent sugars increase growth of a trypanosomatid parasite of bumble bees (v0.1)"
No full textMetaboflux : a method to analyze flux distribution in metabolic networks
No full textInternational audienceTrypanosoma brucei is a parasitic protist of vertebrates that causes sleeping sickness in Africa. A part of its energetic metabolism, including the 6 or 7 first glycolytic step, occurs in an organelle called glycosome. A metabolic pathway for the glycosome had been built by exploiting genomic, reverse genetic and metabolomic data [1]. Some known biological constraints, such as the maintenance of the glycosomal ATP/ADP and NADH/NAD+ balances, have not been carefully addressed in the current model. We propose a modelling approach including structural pathway and metabolic flux analysis to help in the understanding of the system's structure and its semi-quantitative behaviour. We model known biological information with a stochastic Petri net (where transitions are given for the reaction and places for metabolites) where delays can be assigned to transitions given a probability distribution. From a given set of probability distribution representing the flux amount of reactions (the input set of parameters), the simulation of the Petri net allows the exploration of the possible behaviours of the system. At the end of a run, if all input metabolites are consumed, we get concentration for intermediate and output metabolites. We integrate expected metabolites concentrations revealed by biological experiments within an objective function, and use simulated annealing and simplex minimization approach for its global optimization. Therefore, simulations are carried out by fitting the set of input parameters until the system reach the best optimization of the objective function. To explore a large set of possible behaviour of the system, several run of simulations combined with the simulated annealing approach are made. A set of solutions is given by different groups of fluxes distributions (that best fit expected metabolites concentrations), and are helpful to make some assumptions and analysis for a given metabolic system. "Metaboflux" was developed to this purpose and applied to T. brucei. Resulting scenarios strongly argue in favour of an unrealistic NADH/NAD+ imbalance and suggest adding to the model new metabolic pathways. A realistic solution may be to integrate the pentose phosphates to the previous model. The resulting new model was tested with Metaboflux and shows relevant fluxes scenarios. References [1] Bringaud F., Rivière L., Coustou V. (2006) Energy metabolism of trypanosomatids : adaptation to available carbon sources. Molecular and biochemical parasitology. 149: 1-
Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania
No full textTrypanosomatids are unicellular protists that include the human pathogens Leishmania spp. (leishmaniasis), Trypanosoma brucei (sleeping sickness), and Trypanosoma cruzi (Chagas disease). Analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. Using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the Leishmania major genome two new large families of small elements - LmSIDER1 (785 copies) and LmSIDER2 (1,073 copies) - that fulfill all the characteristics of extinct trypanosomatid retroposons. LmSIDERs are ∼70 times more abundant in L. major compared to T. brucei and are found almost exclusively within the 3′-untranslated regions (3′UTRs) of L. major mRNAs. We provide experimental evidence that LmSIDER2 act as mRNA instability elements and that LmSIDER2-containing mRNAs are generally expressed at lower levels compared to the non-LmSIDER2 mRNAs. The considerable expansion of LmSIDERs within 3′UTRs in an organism lacking transcriptional control and their role in regulating mRNA stability indicate that Leishmania have probably recycled these short retroposons to globally modulate the expression of a number of genes. To our knowledge, this is the first example in eukaryotes of the domestication and expansion of a family of mobile elements that have evolved to fulfill a critical cellular function. © 2007 Bringaud et al
The developmental cell biology of Trypanosoma brucei
No full textTrypanosoma brucei provides an excellent system for studies of many aspects of cell biology, including cell structure and morphology, organelle positioning, cell division and protein trafficking. However, the trypanosome has a complex life cycle in which it must adapt either to the mammalian bloodstream or to different compartments within the tsetse fly. These differentiation events require stage-specific changes to basic cell biological processes and reflect responses to environmental stimuli and programmed differentiation events that must occur within a single cell. The organization of cell structure is fundamental to the trypanosome throughout its life cycle. Modulations of the overall cell morphology and positioning of the specialized mitochondrial genome, flagellum and associated basal body provide the classical descriptions of the different life cycle stages of the parasite. The dependency relationships that govern these morphological changes are now beginning to be understood and their molecular basis identified. The overall picture emerging is of a highly organized cell in which the rules established for cell division and morphogenesis in organisms such as yeast and mammalian cells do not necessarily apply. Therefore, understanding the developmental cell biology of the African trypanosome is providing insight into both fundamentally conserved and fundamentally different aspects of the organization of the eukaryotic cell
Identification and stage-specific association with the translational apparatus of TbZFP3, a CCCH protein that promotes trypanosome life-cycle development
No full textThe post-transcriptional control of gene expression is becoming increasingly important in the understanding of regulated events in eukaryotic cells. The parasitic kinetoplastids have a unique reliance on such processes, because their genome is organized into polycistronic transcription units in which adjacent genes are not coordinately regulated. Indeed, the number of RNA-binding proteins predicted to be encoded in the genome of kinetoplastids is unusually large, invoking the presence of unique RNA regulators dedicated to gene expression in these evolutionarily ancient organisms. Here, we report that a small CCCH zinc finger protein, TbZFP3, enhances development between life-cycle stages in Trypanosoma brucei. Moreover, we demonstrate that this protein interacts both with the translational machinery and with other small CCCH proteins previously implicated in trypanosome developmental control. Antibodies to this protein also co-immunoprecipitate EP procyclin mRNA and encode the major surface antigen of insect forms of T. brucei. Strikingly, although TbZFP3 is constitutively expressed, it exhibits developmentally regulated association with polyribosomes, and mutational analysis demonstrates that this association is essential for the expression of phenotype. TbZFP3 is therefore a novel regulator of developmental events in kinetoplastids that acts at the level of the post-transcriptional control of gene expression
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