Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities. | hat (human african trypanosomiasis), caused by the protozoan parasite trypanosoma brucei, is an emerging disease for which new drugs are needed. expression of plasma membrane proteins [e.g. vsg (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by t. brucei. transport of a majority of proteins to the plasma membrane involves their translocation into the er (endoplasmic reticulum). thus inhibition of protein import into the er of t. brucei would be a ... | 2009 | 19196237 |
| prostanoid production in saccharomyces cerevisiae provides a novel assay for nonsteroidal anti-inflammatory drugs. | prostanoids are a large family of lipid mediators originating from prostaglandin h synthase (pghs) activity on the 20-carbon polyunsaturated fatty acids dihomo-gamma-linolenic acid (dgla), arachidonic acid (aa) and eicosapentaenoic acid. the two mouse pghs isoforms, pghs-1 and pghs-2, were expressed in saccharomyces cerevisiae (yeast), as was a signal-peptide-deleted version of pghs-1 (pghs-1ma). pghs-1 showed high activity with both aa and dgla as substrate, whereas pghs-2 activity was high wit ... | 2009 | 19207291 |
| ultrastructural study of golgi duplication in trypanosoma brucei. | golgi duplication in the protozoan parasite trypanosoma brucei has been tracked using serial thin section three-dimensional reconstructions of transmission electron micrographs. the old golgi maintains a constant size (approximately 0.060 microm(3)) throughout the cell cycle. a morphologically identifiable new golgi appears at approximately 0.20 of the cell cycle (defined by the size of the nucleus and lasting about 9 h) and grows from approximately 0.018 microm(3) until it is the same size as t ... | 2009 | 19207482 |
| first small molecular inhibitors of t. brucei dolicholphosphate mannose synthase (dpms), a validated drug target in african sleeping sickness. | drug-like molecules with activity against trypanosoma brucei are urgently required as potential therapeutics for the treatment of african sleeping sickness. starting from known inhibitors of other glycosyltransferases, we have developed the first small molecular inhibitors of dolicholphosphate mannose synthase (dpms), a mannosyltransferase critically involved in glycoconjugate biosynthesis in t. brucei. we show that these dpms inhibitors prevent the biosynthesis of glycosylphosphatidylinositol ( ... | 2009 | 19217283 |
| multiple roles for polypyrimidine tract binding (ptb) proteins in trypanosome rna metabolism. | trypanosomatid genomes encode for numerous proteins containing an rna recognition motif (rrm), but the function of most of these proteins in mrna metabolism is currently unknown. here, we report the function of two such proteins that we have named ptb1 and ptb2, which resemble the mammalian polypyrimidine tract binding proteins (ptb). rnai silencing of these factors indicates that both are essential for life. ptb1 and ptb2 reside mostly in the nucleus, but are found in the cytoplasm, as well. mi ... | 2009 | 19218552 |
| unsaturated mannich bases active against multidrug-resistant trypanosoma brucei brucei strains. | a series of unsaturated mannich bases possessing two electrophilic sites was recently identified as irreversible inhibitors of trypanothione reductase from trypanosoma cruzi. new derivatives were synthesized by modifying the substitution pattern on the aromatic ring and by incorporating the melamine motif of melarsoprol. their affinity to p2 transporter and their trypanocidal properties have been studied using three strains expressing various purine transporters. while the melamine derivatives s ... | 2009 | 19219843 |
| trypanosome tor complex 2 functions in cytokinesis. | tor (target of rapamycin) is a kinase of the phosphatidylinositol kinase-related kinase (pikk) family that controls cell growth in eukaryotes in response to nutrients, energy conditions and growth factors. we have recently identified two trypanosome tor orthologs, named tbtor1 and tbtor2, and two other proteins with significant homology to yeast or mammalian tors, named tbtor-like 1 and tbtor-like 2. tbtor1 depletion results in arrest of bloodstream trypanosomes in g(1), concomitant to protein s ... | 2009 | 19221474 |
| major surface glycoproteins of insect forms of trypanosoma brucei are not essential for cyclical transmission by tsetse. | procyclic forms of trypanosoma brucei reside in the midgut of tsetse flies where they are covered by several million copies of glycosylphosphatidylinositol-anchored proteins known as procyclins. it has been proposed that procyclins protect parasites against proteases and/or participate in tropism, directing them from the midgut to the salivary glands. there are four different procyclin genes, each subject to elaborate levels of regulation. to determine if procyclins are essential for survival an ... | 2009 | 19223969 |
| kinetoplastid guide rna biogenesis is dependent on subunits of the mitochondrial rna binding complex 1 and mitochondrial rna polymerase. | the mitochondrial rna binding complex 1 (mrb1) is a recently discovered complex of proteins associated with the tbrgg1 and tbrgg2 proteins in trypanosoma brucei. based on the phenotype caused by down-regulation of these two proteins, it was proposed to play an unspecified role in rna editing. rnai silencing of three newly characterized protein subunits, guide rna associated proteins (gaps) 1 and 2 as well as a predicted dexd/h-box rna helicase, show they are essential for cell growth in the proc ... | 2009 | 19228586 |
| inhibition of trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites. | dehydroepiandrosterone (dhea) is known as an intermediate in the synthesis of mammalian steroids and a potent uncompetitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (g6pdh), but not the enzyme from plants and lower eukaryotes. g6pdh catalyzes the first step of the pentose-phosphate pathway supplying cells with ribose 5-phosphate, a precursor of nucleic acid synthesis, and nadph for biosynthetic processes and protection against oxidative stress. in this paper we demonstrate that a ... | 2009 | 19231202 |
| leptoclinidamines a-c, indole alkaloids from the australian ascidian leptoclinides durus. | three new indole alkaloids, leptoclinidamines a-c (1-3), were isolated from the australian ascidian leptoclinides durus. their structures were determined by analysis of 2d nmr spectra. leptoclinidamines a and b both contain an indoleglyoxylic acid attached to an l-arginine. the structure of leptoclinidamine a was confirmed by total synthesis. leptoclinidamine c contains the naturally rare 1,3-dimethyl-5-(methylthio)histidine attached to a 6-bromoindole-3-carboxylic acid. leptoclinidamine c (3) a ... | 2009 | 19236031 |
| identification of a palmitoyl acyltransferase required for protein sorting to the flagellar membrane. | protein palmitoylation has diverse effects in regulating protein membrane affinity, localization, binding partner interactions, turnover and function. here, we show that palmitoylation also contributes to the sorting of proteins to the eukaryotic flagellum. african trypanosomes are protozoan pathogens that express a family of unique ca(2+)-binding proteins, the calflagins, which undergo n-terminal myristoylation and palmitoylation. the localization of calflagins depends on their acylation status ... | 2009 | 19240115 |
| a novel function for the atypical small g protein rab-like 5 in the assembly of the trypanosome flagellum. | the atypical small g protein rab-like 5 has been shown to traffic in sensory cilia of caenorhabditis elegans, where it participates in signalling processes but not in cilia construction. in this report, we demonstrate that rabl5 colocalises with intraflagellar transport (ift) proteins at the basal body and in the flagellum matrix of the protist trypanosoma brucei. rabl5 fused to gfp exhibits anterograde movement in the flagellum of live trypanosomes, suggesting it could be associated with ift. a ... | 2009 | 19240117 |
| flagellar membrane localization via association with lipid rafts. | the eukaryotic flagellar membrane has a distinct composition from other domains of the plasmalemma. our work shows that the specialized composition of the trypanosome flagellar membrane reflects increased concentrations of sterols and saturated fatty acids, correlating with direct observation of high liquid order by laurdan fluorescence microscopy. these findings indicate that the trypanosome flagellar membrane possesses high concentrations of lipid rafts: discrete regions of lateral heterogenei ... | 2009 | 19240119 |
| solution structure of urm1 from trypanosoma brucei. | 2009 | 19241476 | |
| differential trypanosome surface coat regulation by a ccch protein that co-associates with procyclin mrna cis-elements. | the genome of trypanosoma brucei is unusual in being regulated almost entirely at the post-transcriptional level. in terms of regulation, the best-studied genes are procyclins, which encode a family of major surface gpi-anchored glycoproteins (ep1, ep2, ep3, gpeet) that show differential expression in the parasite's tsetse-fly vector. although procyclin mrna cis-regulatory sequences have provided the paradigm for post-transcriptional control in kinetoplastid parasites, trans-acting regulators of ... | 2009 | 19247446 |
| targeted delivery of compounds to trypanosoma brucei using the melamine motif. | there is an urgent need for the development of new drugs for the treatment of human african trypanosomiasis. the causative organism, trypanosoma brucei, has been shown to have some unusual plasma membrane transporters, in particular the p2 aminopurine transporter and related permeases, which have been used for the selective targeting of trypanocidal compounds to the organism. in this paper, we report the addition of melamine-based p2-targeting motifs to three different classes of compound in ord ... | 2009 | 19250832 |
| a type iii protein arginine methyltransferase from the protozoan parasite trypanosoma brucei. | arginine methylation is a widespread post-translational modification of proteins catalyzed by a family of protein arginine methyltransferases (prmts). the ancient protozoan parasite, trypanosoma brucei, possesses five putative prmts, a relatively large number for a single-celled eukaryote. trypanosomatids lack gene regulation at the level of transcription, instead relying on post-transcriptional control mechanisms that act at the levels of rna turnover, translation, and editing, all processes th ... | 2009 | 19254949 |
| pentamidine movement across the murine blood-brain and blood-cerebrospinal fluid barriers: effect of trypanosome infection, combination therapy, p-glycoprotein, and multidrug resistance-associated protein. | during the first stage of human african trypanosomiasis (hat), trypanosoma brucei gambiense is found mainly in the blood, and pentamidine treatment is used. pentamidine is predominantly ineffective once the parasites have invaded the central nervous system (cns). this lack of efficacy is thought to be due to the inability of pentamidine to cross the blood-brain barrier, although this has never been explored directly. this study addresses this using brain perfusion in healthy mice, p-glycoprotein ... | 2009 | 19261919 |
| the canonical pathway for selenocysteine insertion is dispensable in trypanosomes. | the micronutrient selenium is found in proteins as selenocysteine (sec), the 21st amino acid cotranslationally inserted in response to a uga codon. in vitro studies in archaea and mouse showed that sec-trna(sec) formation is a 3-step process starting with serylation of trna(sec) by seryl-trna synthetase (serrs), phosphorylation of serine to form phosphoserine (sep)-trna(sec) by phosphoseryl-trna(sec) kinase (pstk), and conversion to sec-trna(sec) by sep-trna:sec-trna synthase (sepsecs). however, ... | 2009 | 19279205 |
| identification of total and differentially expressed excreted-secreted proteins from trypanosoma congolense strains exhibiting different virulence and pathogenicity. | animal trypanosomosis is a major constraint to livestock productivity in the tropics and has a significant impact on the life of millions of people globally (mainly in africa, south america and south-east asia). in africa, the disease in livestock is caused mainly by trypanosoma congolense, trypanosoma vivax, trypanosoma evansi and trypanosoma brucei brucei. the extracellular position of trypanosomes in the bloodstream of their host requires consideration of both the parasite and its naturally e ... | 2009 | 19285981 |
| novel s-adenosylmethionine decarboxylase inhibitors for the treatment of human african trypanosomiasis. | trypanosomiasis remains a significant disease across the sub-saharan african continent, with 50,000 to 70,000 individuals infected. the utility of current therapies is limited by issues of toxicity and the need to administer compounds intravenously. we have begun a program to pursue lead optimization around mdl 73811, an irreversible inhibitor of s-adenosylmethionine decarboxylase (adometdc). this compound is potent but in previous studies cleared rapidly from the blood of rats (t. l. byers, t. ... | 2009 | 19289530 |
| three-dimensional cellular architecture of the flagellar pocket and associated cytoskeleton in trypanosomes revealed by electron microscope tomography. | this study uses electron tomography linked to a variety of other em methods to provide an integrated view of the flagellar pocket and basal body area of the african trypanosome procyclic trypomastigote. we reveal the pocket as an asymmetric membranous 'balloon' with two boundary structures. one of these - the collar - defines the flagellum exit point. the other defines the entry point of the flagellum into the pocket and consists of both an internal transitional fibre array and an external membr ... | 2009 | 19299460 |
| rna interference-mediated silencing of ornithine decarboxylase and spermidine synthase genes in trypanosoma brucei provides insight into regulation of polyamine biosynthesis. | polyamine biosynthesis is a drug target for the treatment of african sleeping sickness; however, mechanisms regulating the pathway in trypanosoma brucei are not well understood. recently, we showed that rna interference (rnai)-mediated gene silencing or the inhibition of s-adenosylmethionine decarboxylase (adometdc) led to the upregulation of the adometdc activator, prozyme, and ornithine decarboxylase (odc) proteins. to determine if this regulatory response is specific to adometdc, we studied t ... | 2009 | 19304951 |
| synthetic nonamer peptides derived from insect defensin mediate the killing of african trypanosomes in axenic culture. | synthetic antimicrobial 9-mer peptides (designated as peptides a and b) designed on the basis of insect defensins and their effects on the growth of african trypanosomes were examined using two isolates of trypanosoma congolense, il1180 and il3338, and two isolates of trypanosoma brucei brucei, iltat1.1and gutat 3.1, under axenic culture conditions. both peptides inhibited the growth of all bloodstream form (bsf) trypanosomes at 200-400 microg/ml in the complete growth medium, with peptide a bei ... | 2009 | 19308456 |
| lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an x-ray and nmr investigation. | considerable effort has focused on the development of selective protein farnesyl transferase (ftase) and protein geranylgeranyl transferase (ggtase) inhibitors as cancer chemotherapeutics. here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (fpps) and geranylgeranyl diphosphate synthase (ggpps), the two enzymes upstream of ftase and ggtase, by lipophilic bisphosphonates. due to dual site targeting and decreased polarity, the comp ... | 2009 | 19309137 |
| drug screening by crossing membranes: a novel approach to identification of trypanocides. | trypanosomes are a group of protozoan parasites that inflict huge health and economic burdens across the globe. the african trypanosome, trypanosoma brucei, the causative agent of sleeping sickness, has a highly sophisticated mechanism of antigenic variation that facilitates chronic survival in the mammalian host, and also all but eliminates any realistic hope for vaccination-based control. however, trypanosomes are also highly divergent organisms, with many biochemical processes setting them ap ... | 2009 | 19309311 |
| differential functions of two editosome exouases in trypanosoma brucei. | mitochondrial rnas in trypanosomes are edited by the insertion and deletion of uridine (u) nucleotides to form translatable mrnas. editing is catalyzed by three distinct editosomes that contain two related u-specific exonucleases (exouases), krex1 and krex2, with the former present exclusively in kren1 editosomes and the latter present in all editosomes. we show here that repression of krex1 expression leads to a concomitant reduction of kren1 in approximately 20s editosomes, whereas krex2 repre ... | 2009 | 19318463 |
| functional characterization and protein-protein interactions of trypanosome splicing factors u2af35, u2af65 and sf1. | early in the assembly of eukaryotes the branch-point binding protein (bbp, also called sf1) recognizes the branch point sequence, whereas the heterodimer u2af, consisting of a 65 and a 35 kda subunit, contacts the polypyrimidine tract and the ag splice site, respectively. herein, we identified, cloned and expressed the trypanosoma cruzi and trypanosoma brucei u2af35, u2af65 and sf1. trypanosomatid u2af65 strongly diverged from yeast and human homologues. on the contrary, trypanosomatid sf1 was c ... | 2009 | 19320097 |
| the cell cycle as a therapeutic target against trypanosoma brucei: hesperadin inhibits aurora kinase-1 and blocks mitotic progression in bloodstream forms. | aurora kinase family members co-ordinate a range of events associated with mitosis and cytokinesis. anti-cancer therapies are currently being developed against them. here, we evaluate whether aurora kinase-1 (tbauk1) from pathogenic trypanosoma brucei might be targeted in anti-parasitic therapies as well. conditional knockdown of tbauk1 within infected mice demonstrated its essential contribution to infection. an in vitro kinase assay was developed which used recombinant trypanosome histone h3 a ... | 2009 | 19320832 |
| membrane permeabilization by trypanosome lytic factor, a cytolytic human high density lipoprotein. | trypanosome lytic factor (tlf) is a subclass of human high density lipoprotein (hdl) that mediates an innate immune killing of certain mammalian trypanosomes, most notably trypanosoma brucei brucei, the causative agent of a wasting disease in cattle. mechanistically, killing is initiated in the lysosome of the target trypanosome where the acidic ph facilitates a membrane-disrupting activity by tlf. here we utilize a model liposome system to characterize the membrane binding and permeabilizing ac ... | 2009 | 19324878 |
| evaluation of anti-sleeping-sickness drugs and topoisomerase inhibitors in combination on trypanosoma brucei. | 2009 | 19336455 | |
| the fip-1 like polyadenylation factor in trypanosomes and the structural basis for its interaction with cpsf30. | in trypanosomes transcription is polycistronic and individual mrnas are generated by a trans-splicing/polyadenylation coupled reaction. we identified a divergent trypanosome fip1-like, a factor required for mrna 3' end formation from yeasts to human. here we showed that it is a nuclear protein with a speckled distribution essential for trypanosome viability. a strong interaction was found between tcfip1-like and tccpsf30, a component of the polyadenylation complex. we determined the specific ami ... | 2009 | 19338765 |
| kynurenine pathway inhibition reduces central nervous system inflammation in a model of human african trypanosomiasis. | human african trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites trypanosoma brucei rhodesiense or trypanosoma brucei gambiense, and is a major cause of systemic and neurological disability throughout sub-saharan africa. following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. treatment of human african trypanosomiasis currently relies on a limited number of h ... | 2009 | 19339256 |
| solution structure of sumo from trypanosoma brucei and its interaction with ubc9. | 2009 | 19343802 | |
| antitrypanosomal activity of some pregnane glycosides isolated from caralluma species. | pregnane glycosides previously isolated from genus caralluma (c. penicillata, c. tuberculata and c. russelliana) were tested for their antitrypanosomal activity. penicilloside e showed the highest antitrypanosomal activity (ic(50) 1.01 microg/ml) followed by caratuberside c (ic(50) 1.85 microg/ml), which exhibited the highest selectivity index (si 12.04). it was noticed that acylation is required for the antitrypanosomal activity while glycosylation at c-20 has no significant effect on the activ ... | 2009 | 19345077 |
| rap1 is essential for silencing telomeric variant surface glycoprotein genes in trypanosoma brucei. | trypanosoma brucei expresses variant surface glycoprotein (vsg) genes in a strictly monoallelic fashion in its mammalian hosts, but it is unclear how this important virulence mechanism is enforced. telomere position effect, an epigenetic phenomenon, has been proposed to play a critical role in vsg regulation, yet no telomeric protein has been identified whose disruption led to vsg derepression. we now identify tbrap1 as an intrinsic component of the t. brucei telomere complex and a major regulat ... | 2009 | 19345190 |
| insights into the enzymatic mechanism of 6-phosphogluconolactonase from trypanosoma brucei using structural data and molecular dynamics simulation. | trypanosoma brucei is the causative agent of african sleeping sickness. current work for the development of new drugs against this pathology includes evaluation of enzymes of the pentose phosphate pathway (ppp), which first requires a clear understanding of their function and mechanism of action. in this context, we focused on t. brucei 6-phosphogluconolactonase (tb6pgl), which converts delta-6-phosphogluconolactone into 6-phosphogluconic acid in the second step of the ppp. we have determined th ... | 2009 | 19345229 |
| the phosphoproteome of bloodstream form trypanosoma brucei, causative agent of african sleeping sickness. | the protozoan parasite trypanosoma brucei is the causative agent of human african sleeping sickness and related animal diseases, and it has over 170 predicted protein kinases. protein phosphorylation is a key regulatory mechanism for cellular function that, thus far, has been studied in t.brucei principally through putative kinase mrna knockdown and observation of the resulting phenotype. however, despite the relatively large kinome of this organism and the demonstrated essentiality of several t ... | 2009 | 19346560 |
| both type-i and type-ii responses contribute to murine trypanotolerance. | the host immune system has been documented to influence the course and outcome of infection with the phospholipase-c-deficient (plc(-/-)) trypanosoma brucei brucei. we addressed the resistant mechanisms during trypanosomosis by comparing the immune response to variant-specific surface glycoprotein (vsg) in relatively susceptible c3h mice and trypanotolerant (c57bl/6 x balb/c)-f1 (b6b-f1) mice infected with plc(-/-) parasites. during the early stage of infection, lymphoid cells from both plc(-/-) ... | 2009 | 19346699 |
| genetics. leishmania exploit sex. | 2009 | 19359570 | |
| four histone variants mark the boundaries of polycistronic transcription units in trypanosoma brucei. | unusually for a eukaryote, genes transcribed by rna polymerase ii (pol ii) in trypanosoma brucei are arranged in polycistronic transcription units. with one exception, no pol ii promoter motifs have been identified, and how transcription is initiated remains an enigma. t. brucei has four histone variants: h2az, h2bv, h3v, and h4v. using chromatin immunoprecipitation (chip) and sequencing (chip-seq) to examine the genome-wide distribution of chromatin components, we show that histones h4k10ac, h2 ... | 2009 | 19369410 |
| a yeast-endonuclease-generated dna break induces antigenic switching in trypanosoma brucei. | trypanosoma brucei is the causative agent of african sleeping sickness in humans and one of the causes of nagana in cattle. this protozoan parasite evades the host immune system by antigenic variation, a periodic switching of its variant surface glycoprotein (vsg) coat. vsg switching is spontaneous and occurs at a rate of about 10(-2)-10(-3) per population doubling in recent isolates from nature, but at a markedly reduced rate (10(-5)-10(-6)) in laboratory-adapted strains. vsg switching is thoug ... | 2009 | 19369939 |
| homology modeling and molecular dynamics simulation of n-myristoyltransferase from protozoan parasites: active site characterization and insights into rational inhibitor design. | myristoyl-coa:protein n-myristoyltransferase (nmt) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-coa to the n-terminal glycine of a number of eukaryotic cellular and viral proteins. recent experimental data suggest nmt from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. however, the active site topology and inhibitor specificity of these enzymes remain unclear. in this study, thre ... | 2009 | 19370313 |
| comparative molecular docking of antitrypanosomal natural products into multiple trypanosoma brucei drug targets. | antitrypanosomal natural products with different structural motifs previously shown to have growth inhibitory activity against trypanosoma brucei were docked into validated drug targets of the parasite, which include trypanothione reductase, rhodesain, farnesyl diphosphate synthase, and triosephosphate isomerase. the in-silico calculations predicted that lowest energy docked poses of a number of the compounds can interact with catalysis-dependent residues, thus making them possible catalytic inh ... | 2009 | 19384282 |
| systematic structural studies of iron superoxide dismutases from human parasites and a statistical coupling analysis of metal binding specificity. | superoxide dismutases (sods) are a crucial class of enzymes in the combat against intracellular free radical damage. they eliminate superoxide radicals by converting them into hydrogen peroxide and oxygen. in spite of their very different life cycles and infection strategies, the human parasites plasmodium falciparum, trypanosoma cruzi and trypanosoma brucei are known to be sensitive to oxidative stress. thus the parasite fe-sods have become attractive targets for novel drug development. here we ... | 2009 | 19384994 |
| the aignopsanes, a new class of sesquiterpenes from selected chemotypes of the sponge cacospongia mycofijiensis. | a survey of individual specimens of northern papua new guinea derived cacospongia mycofijiensis has yielded novel sesquiterpenes, aignopsanoic acid a (1), methyl aignopsanoate a (2), and isoaignopsanoic acid a (3). the structures and absolute configurations of 1-3 were established using nmr data, x-ray crystallography results, and an analysis of cd properties. two of these metabolites, 1 and 2, were moderately active against trypanosoma brucei, the parasite responsible for sleeping sickness. | 2009 | 19385671 |
| dual targeting of a trnaasp requires two different aspartyl-trna synthetases in trypanosoma brucei. | the mitochondrion of the parasitic protozoon trypanosoma brucei does not encode any trnas. this deficiency is compensated for by partial import of nearly all of its cytosolic trnas. most trypanosomal aminoacyl-trna synthetases are encoded by single copy genes, suggesting the use of the same enzyme in the cytosol and in the mitochondrion. however, the t. brucei genome encodes two distinct genes for eukaryotic aspartyl-trna synthetase (asprs), although the cell has a single trnaasp isoacceptor onl ... | 2009 | 19386587 |
| transcriptionally active tfiih of the early-diverged eukaryote trypanosoma brucei harbors two novel core subunits but not a cyclin-activating kinase complex. | trypanosoma brucei is a member of the early-diverged, protistan family trypanosomatidae and a lethal parasite causing african sleeping sickness in humans. recent studies revealed that t. brucei harbors extremely divergent orthologues of the general transcription factors tbp, tfiia, tfiib and tfiih and showed that these factors are essential for initiating rna polymerase ii-mediated synthesis of spliced leader (sl) rna, a trans splicing substrate and key molecule in trypanosome mrna maturation. i ... | 2009 | 19386623 |
| perturbation of phosphatidylethanolamine synthesis affects mitochondrial morphology and cell-cycle progression in procyclic-form trypanosoma brucei. | phosphatidylethanolamine (pe) and phosphatidylcholine (pc) are the two major constituents of eukaryotic cell membranes. in the protist trypanosoma brucei, pe and pc are synthesized exclusively via the kennedy pathway. to determine which organelles or processes are most sensitive to a disruption of normal phospholipid levels, the cellular consequences of a decrease in the levels of pe or pc, respectively, were studied following rnai knock-down of four enzymes of the kennedy pathway. rnai against ... | 2009 | 19400804 |
| towards a new reference test for surra in camels. | current serological diagnosis of trypanosoma evansi infection in camels is based on the native variable antigen type rotat 1.2. the goal of this study was to develop a novel serological diagnostic test based on a nonvariable protein and freed from the use of rats or mice for its production. an enzyme-linked immunosorbent assay using a recombinant extracellular domain of invariant surface glycoprotein 75 (elisa/risg75) was developed and tested on a collection of 184 camel sera. the results were c ... | 2009 | 19403780 |
| in vitro and in vivo antitrypanosomal activities of three peptide antibiotics: leucinostatin a and b, alamethicin i and tsushimycin. | in the course of our screening for antitrypanosomal compounds from soil microorganisms, as well as from the antibiotics library of the kitasato institute for life sciences, we found three peptide antibiotics, leucinostatin (a and b), alamethicin i and tsushimycin, which exhibited potent or moderate antitrypanosomal activity. we report here the in vitro and in vivo antitrypanosomal properties and cytotoxicities of leucinostatin a and b, alamethicin i and tsushimycin compared with suramin. we also ... | 2009 | 19407848 |
| effects of melarsamine hydrochloride (cymelarsan) and diminazene aceturate (berenil) on the pathology of experimental trypanosoma brucei infection in red fronted gazelles (gazella rufifrons). | an experimental infection of red fronted gazelles (gazella rufifrons) with trypanosoma brucei strain mkar/84/nitr/6 was carried out. two waves of parasitaemia which corresponded with a significant decline (p<0.05) in packed cell volume (pcv) was encountered in the infected untreated controls and those treated at day 8 post-infection with a sub-optimal dosage of diminazene aceturate (berenil) at 3.5 mg/kg body weight. at postmortem, hepatomegally, splenomegally, lymphadenopathy, nephritis, myocar ... | 2009 | 19410371 |
| electron microscopy and cytochemistry analysis of the endocytic pathway of pathogenic protozoa. | endocytosis is essential for eukaryotic cell survival and has been well characterized in mammal and yeast cells. among protozoa it is also important for evading from host immune defenses and to support intense proliferation characteristic of some life cycle stages. here we focused on the contribution of morphological and cytochemical studies to the understanding of endocytosis in trichomonas, giardia, entamoeba, plasmodium, and trypanosomatids, mainly trypanosoma cruzi, and also trypanosoma bruc ... | 2009 | 19410686 |
| the single enth-domain protein of trypanosomes; endocytic functions and evolutionary relationship with epsin. | epsin n-terminal homology (enth) domains occur in proteins of either the epsin or epsin-related (epsinr) form. they principally function in clathrin-mediated trafficking and membrane deformation. both epsin and epsinr possess clathrin-binding motifs, but only epsin incorporates a ubiquitin-interaction motif (uim). to better understand the origins of enth-domain proteins and their functions, we performed detailed comparative genomics and phylogenetics on the epsin family. the epsin enth-uim confi ... | 2009 | 19416477 |
| chromatin-based transcriptional punctuation. | the long polycistronic transcription units of trypanosomes do not appear to be demarcated by the usual dna motifs that punctuate transcription in familiar eukaryotes. in this issue of genes & development, siegel and colleagues (pp. 1063-1076) describe a system for the demarcation of trypanosome transcription units based on the deposition and turnover of histone variants rather than on the binding of transcription factors. replication-independent incorporation of histone variants and destabilizat ... | 2009 | 19417102 |
| discovery of new s-adenosylmethionine decarboxylase inhibitors for the treatment of human african trypanosomiasis (hat). | modification of the structure of trypanosomal adometdc inhibitor 1 (mdl73811) resulted in the identification of a new inhibitor 7a, which features a methyl substituent at the 8-position. compound 7a exhibits improved potencies against both the trypanosomal adometdc enzyme and parasites, and better blood brain barrier penetration than 1. | 2009 | 19419862 |
| stability of loop-mediated isothermal amplification (lamp) reagents and its amplification efficiency on crude trypanosome dna templates. | this study evaluated the stability of lamp reagents when stored at 25 degrees c and 37 degrees c, and also assessed its detection efficiency on different dna template preparations. accordingly, lamp using reagents stored at 25 degrees c and 37 degrees c amplified dna of in vitro cultured t. b. brucei (gutat 3.1) from day 1 to day 15 of reagent storage. there were no significant differences (p>0.05) in detection sensitivity of lamp among the reagents stored at 25 degrees c, 37 degrees c and -20 d ... | 2009 | 19420851 |
| design and synthesis of trypanosoma brucei active 1-alkyloxy and 1-benzyloxyadamantano 2-guanylhydrazones. | treating african trypanosomiasis: the synthesis and biological evaluation of novel 1-alkyloxy and 1-benzyloxyadamantano 2-guanylhydrazones, their 1-dioxa congeners and two 1-benzyladamantano 2-guanylhydrazones is reported. preliminary structure-activity relationship data were elucidated and lead compounds suitable for further optimization were discovered. | 2009 | 19422003 |
| spliceosomal proteomics in trypanosoma brucei reveal new rna splicing factors. | in trypanosomatid parasites, spliced leader (sl) trans splicing is an essential nuclear mrna maturation step which caps mrnas posttranscriptionally and, in conjunction with polyadenylation, resolves individual mrnas from polycistronic precursors. while all trypanosomatid mrnas are trans spliced, intron removal by cis splicing is extremely rare and predicted to occur in only four pre-mrnas. trans- and cis-splicing reactions are carried out by the spliceosome, which consists of u-rich small nuclea ... | 2009 | 19429779 |
| the antiprotozoal activity of sixteen asteraceae species native to sudan and bioactivity-guided isolation of xanthanolides from xanthium brasilicum. | in vitro screening of the dichloromethane extracts of 16 asteraceae species native to sudan for activity against major protozoan pathogens revealed that a xanthium brasilicum vell. [syn. x. strumarium var. brasilicum (vell.) baker in mart.] extract was the most active against trypanosoma brucei rhodesiense, the etiological agent of east african human trypanosomiasis (ic(50) = 0.1 microg/ml). this plant extract also exhibited noticeable activities against t. cruzi (chagas disease), leishmania don ... | 2009 | 19431098 |
| the f(0)f(1)-atp synthase complex contains novel subunits and is essential for procyclic trypanosoma brucei. | the mitochondrial f(0)f(1) atp synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in trypanosoma brucei, an early diverged eukaryotic pathogen. we purified the f(0)f(1) atp synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. we identified 22 proteins of which five are related to f(1) subunits, three to f( ... | 2009 | 19436713 |
| purification and biochemical characterization of lysosomal acid phosphatases (ec 3.1.3.2) from blood stream forms, trypanosoma brucei brucei. | three acid phosphatases (acp) were isolated and characterized from the lysosomes of blood stream forms of trypanosoma brucei by a combination of isopynic and differential centrifugation through ficoll, organic solvent precipitation, ion exchange on deae cellulose 52 and size exclusion chromatography on sephadex g-75 columns. the purified acp emerged as three distinct peaks (acp i, acp ii and acp iii) with high specific activities and they moved homogeneously on 12% sds-page each as a single band ... | 2009 | 19442761 |
| functional characterization of stage-specific aminotransferases from trypanosomatids. | as part of a study on aminotransferases, genes coding for putative enzymes from trypanosoma brucei and leishmania major (alanine aminotransferases: alats, tb927.1.3950 and lmjf12.0630; kynurenine aminotransferase: kat, tb10.389.1810; and tyrosine aminotransferase: tat, lmjf36.2360) were cloned and functionally expressed in escherichia coli. the putative t. brucei kat, in fact coded for a glutamine aminotransferase (glnat), which exhibited a notably high affinity (in the micromolar range) towards ... | 2009 | 19443056 |
| complex interactions in the regulation of trypanosome mitochondrial gene expression. | trypanosomes undergo extreme physiological changes to adapt to different environments as they cycle between hosts. adaptation to the different environments has evolved an energy metabolism involving a mitochondrion with an unusual genome. recently, aphasizhev and colleagues have identified two new protein complexes, a mitochondrial polyadenylation complex and a guide rna stabilization complex, that provide novel insights into the coordinated expression of the mitochondrial genome. | 2009 | 19443271 |
| molecular microbiology: a key event in survival. | 2009 | 19444197 | |
| microbiology: signals for change. | 2009 | 19444199 | |
| a surface transporter family conveys the trypanosome differentiation signal. | microbial pathogens use environmental cues to trigger the developmental events needed to infect mammalian hosts or transmit to disease vectors. the parasites causing african sleeping sickness respond to citrate or cis-aconitate (cca) to initiate life-cycle development when transmitted to their tsetse fly vector. this requires hypersensitization of the parasites to cca by exposure to low temperature, conditions encountered after tsetse fly feeding at dusk or dawn. here we identify a carboxylate-t ... | 2009 | 19444208 |
| nutritional stress of adult female tsetse flies (diptera: glossinidae) affects the susceptibility of their offspring to trypanosomal infections. | the epidemiology of tsetse-transmitted trypanosomiasis depends, among other factors, on the proportion of infected flies in a tsetse population. a wide range of intrinsic and extrinsic factors seem to determine the ability of a tsetse fly to become infected and to transmit the parasite. in this paper, we investigated the effect of nutritional stress of reproducing female glossina morsitans morsitans on the susceptibility of their offspring to trypanosomal infections. adult female flies that were ... | 2009 | 19445895 |
| the bilobe structure of trypanosoma brucei contains a morn-repeat protein. | the golgi of the kinetoplastid parasite trypanosoma brucei is closely apposed to a bilobe structure containing tbcentrin2 and tbcentrin4 in procyclic cells. however, both are additionally localized to the basal bodies. here we report the characterization of a membrane occupation and recognition nexus (morn)-repeat protein, tbmorn1, present at the bilobe but not at the basal body. the anterior part of the tbmorn1 structure partially overlapped with the flagellar attachment zone while the posterio ... | 2009 | 19445968 |
| uridine insertion/deletion rna editing in trypanosomatid mitochondria: in search of the editosome. | the rna ligase-containing or l-complex is the core complex involved in uridine insertion/deletion rna editing in trypanosome mitochondria. blue native gels of glycerol gradient-separated fractions of mitochondrial lysate from cells transfected with the tap-tagged editing protein, lc-8 (tbmp44/krepb5), show a approximately 1 mda l-complex band and, in addition, two minor higher molecular weight rel1-containing complexes: one (l*a) co-sedimenting with the l-complex and running in the gel at around ... | 2009 | 19447916 |
| gene organization and sequence analyses of transfer rna genes in trypanosomatid parasites. | the protozoan pathogens leishmania major, trypanosoma brucei and trypanosoma cruzi (the tritryps) are parasites that produce devastating human diseases. these organisms show very unusual mechanisms of gene expression, such as polycistronic transcription. we are interested in the study of trna genes, which are transcribed by rna polymerase iii (pol iii). to analyze the sequences and genomic organization of trna genes and other pol iii-transcribed genes, we have performed an in silico analysis of ... | 2009 | 19450263 |
| casein kinase 1 isoform 2 is essential for bloodstream form trypanosoma brucei. | induction of rna interference targeted against casein kinase 1 isoform 2 (tbck1.2, tb927.5.800) in bloodstream form trypanosoma brucei in vitro results in rapid cessation of growth, gross morphological changes, multinucleation and ultimately cell death. a null mutant of the highly homologous casein kinase 1 isoform 1 (tb927.5.790) in bloodstream form t. brucei displays no growth or morphological phenotype in vitro. a truncated form of tbck1.2 expressed in escherichia coli as a gst fusion produce ... | 2009 | 19450734 |
| drbd1 is the trypanosoma brucei homologue of the spliceosome-associated protein 49. | the 5'-ends of all kinetoplastid mrnas consist of a short sequence added by trans splicing. in contrast to cis splicing in mammals, trans splicing in trypanosomes does not involve sequence-specific recognition of the branch point by the u2 snrnp. in mammalian cells and yeast, u2 snrnp is associated with the multimeric factor sf3b, which contains p14, sf3b10, sf3b14b, sap49, sap130, sap145 and sap155. the interaction between trypanosoma cruzi p14 and sap155 has already been characterised using th ... | 2009 | 19450735 |
| identification of core components of the exon junction complex in trypanosomes. | in animal cells, the exon junction complex (ejc) is deposited onto mrnas during the second step of splicing, 20-24 nt upstream of the exon-exon junction. the ejc core contains four proteins: mago, y14, eif4aiii and btz. in trypanosomes, cis-splicing is very rare but all mrnas are subject to 5'trans-splicing of a 39-nt rna sequence. here we show that trypanosomes have a conserved mago and a divergent y14 protein, but we were unable to identify a btz orthologue. we demonstrate that mago and y14 fo ... | 2009 | 19450736 |
| trypanocidal activity of 8-methyl-5'-{[(z)-4-aminobut-2-enyl]-(methylamino)}adenosine (genz-644131), an adenosylmethionine decarboxylase inhibitor. | genzyme 644131, 8-methyl-5'-{[(z)-4-aminobut-2-enyl](methylamino)}adenosine, is an analog of the enzyme activated s-adenosylmethionine decarboxylase (adometdc) inhibitor and the trypanocidal agent mdl-7381, 5-{[(z)-4-aminobut-2-enyl](methylamino)}adenosine. the analog differs from the parent in having an 8-methyl group on the purine ring that bestows favorable pharmacokinetic, biochemical, and trypanocidal activities. the compound was curative in acute trypanosoma brucei brucei and drug-resistan ... | 2009 | 19451291 |
| site-specific dna double-strand breaks greatly increase stable transformation efficiency in trypanosoma brucei. | genetic manipulation in african trypanosomes typically relies upon electroporation with chromosomal integration of dna constructs by homologous recombination. relatively little is known about chromosomal recombination and repair in these organisms however and low transformation efficiency and position effects can limit forward genetic approaches. in yeast and mammalian cells, site-specific dna double-strand breaks (dsbs) stimulate targeted integration through homologous recombination-based repai ... | 2009 | 19459229 |
| mitochondrial carrier family inventory of trypanosoma brucei brucei: identification, expression and subcellular localisation. | the mitochondrial carrier family (mcf) is a group of structurally conserved proteins that mediate the transport of a wide range of metabolic intermediates across the mitochondrial inner membrane. in this paper, an overview of the mitochondrial carrier proteins (mcps) of the early-branching kinetoplastid parasite trypanosoma brucei brucei is presented. sequence analysis and phylogenetic reconstruction gave insight into the evolution and conservation of the 24 identified tbmcps; for most of these, ... | 2009 | 19463859 |
| mitochondrial trna import in trypanosoma brucei is independent of thiolation and the rieske protein. | due to a complete lack of the trna genes in the mitochondrial genome of trypanosoma brucei, all trnas needed for mitochondrial translation have to be imported into the organelle from the cytosol. a previous study showed that the modified nucleotide s(2)u could act as a negative determinant for mitochondrial trna import in another kinetoplastid, leishmania tarentolae. we have investigated whether the same type of cytosolic control for trna retention exists in t. brucei. based on northern analysis ... | 2009 | 19465685 |
| novel tutase associates with an editosome-like complex in mitochondria of trypanosoma brucei. | expression of mitochondrial genomes in kinetoplastida protists requires massive uracil insertion/deletion mrna editing. the cascade of editing reactions is accomplished by a multiprotein complex, the 20s editosome, and is directed by trans-acting guide rnas. two distinct rna terminal uridylyl transferases (tutases), rna editing tutase 1 (ret1) and rna editing tutase 2 (ret2), catalyze 3' uridylylation of guide rnas and u-insertions into the mrnas, respectively. ret1 is also involved in mitochond ... | 2009 | 19465686 |
| the glycosylphosphatidylinositol-plc in trypanosoma brucei forms a linear array on the exterior of the flagellar membrane before and after activation. | bloodstream forms of trypanosoma brucei contain a glycosylphosphatidylinositol-specific phospholipase c (gpi-plc) that cleaves the gpi-anchor of the variable surface glycoprotein (vsg). its location in trypanosomes has been controversial. here, using confocal microscopy and surface labelling techniques, we show that the gpi-plc is located exclusively in a linear array on the outside of the flagellar membrane, close to the flagellar attachment zone, but does not co-localize with the flagellar att ... | 2009 | 19503825 |
| hypermethylated cap 4 maximizes trypanosoma brucei translation. | through trans-splicing of a 39-nt spliced leader (sl) onto each protein-coding transcript, mature kinetoplastid mrna acquire a hypermethylated 5'-cap structure, but its function has been unclear. gene deletions for three trypanosoma brucei cap 2'-o-ribose methyltransferases, tbmtr1, tbmtr2 and tbmtr3, reveal distinct roles for four 2'-o-methylated nucleotides. elimination of individual gene pairs yields viable cells; however, attempts at double knock-outs resulted in the generation of a tbmtr2-/ ... | 2009 | 19504740 |
| antitrypanosomal and cytotoxic activities of pyrrolizidine alkaloid-producing plants of ethiopia. | the objective was to determine the in-vitro effect of extracts from 19 ethiopian plant species and four pure pyrrolizidine alkaloids on bloodstream forms of trypanosoma brucei brucei and human leukaemia hl-60 cells. | 2009 | 19505372 |
| gene conversion transfers the gaf-a domain of phosphodiesterase tbrpdeb1 to one allele of tbrpdeb2 of trypanosoma brucei. | chromosome 9 of trypanosoma brucei contains two closely spaced, very similar open reading frames for cyclic nucleotide specific phosphodiesterases tbrpdeb1 and tbrpdeb2. they are separated by 2379 bp, and both code for phosphodiesterases with two gaf domains in their n-terminal moieties and a catalytic domain at the c-terminus. | 2009 | 19513125 |
| a novel 1-indanone isolated from uvaria afzelii roots. | bioactivity-guided fractionations of chloromethylenic extract of the roots of u. afzelii (annonaceae), using leishmania donovani and trypanosoma brucei brucei bioassay, resulted in the isolation of the two known compounds, emorydone (1) and demethoxymatteucinol (2), previously isolated from the stems, which were characterised from this source. in addition, the novel 1-indanone, afzeliindanone (3), was also isolated. the structure determination of afzeliindanone (3) was elucidated on the basis of ... | 2009 | 19521904 |
| cross-species activation of trypanosome s-adenosylmethionine decarboxylase by the regulatory subunit prozyme. | the protozoan parasite trypanosoma cruzi is the causative agent of chagas disease (american trypanosomiasis), a neglected disease of central and south america. polyamines are small organic cations that are required for cell growth and their biosynthesis has been the target of drug discovery efforts in both t. cruzi and the related trypanosoma brucei parasites. here we show that, as previously demonstrated for t. brucei, s-adenosylmethionine decarboxylase (adometdc) from t. cruzi forms a heterodi ... | 2009 | 19523496 |
| evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor. | the nuclear pore complex (npc) is a macromolecular assembly embedded within the nuclear envelope that mediates bidirectional exchange of material between the nucleus and cytoplasm. our recent work on the yeast npc has revealed a simple modularity in its architecture and suggested a common evolutionary origin of the npc and vesicle coating complexes in a progenitor protocoatomer. however, detailed compositional and structural information is currently only available for vertebrate and yeast npcs, ... | 2009 | 19525551 |
| one scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening. | the enzyme pteridine reductase 1 (ptr1) is a potential target for new compounds to treat human african trypanosomiasis. a virtual screening campaign for fragments inhibiting ptr1 was carried out. two novel chemical series were identified containing aminobenzothiazole and aminobenzimidazole scaffolds, respectively. one of the hits (2-amino-6-chloro-benzimidazole) was subjected to crystal structure analysis and a high resolution crystal structure in complex with ptr1 was obtained, confirming the p ... | 2009 | 19527033 |
| secondary bacterial infection in plasma endotoxin levels and the acute-phase response of mice infected with trypanosoma brucei brucei. | murine trypanosoma brucei brucei infection leads to elevated plasma endotoxin-like activity levels not related to parasitaemia levels accompanied by the development of acute-phase response and increased plasma levels of serum amyloid p (sap) and haptoglobin (hp). to determine the source of the endotoxin-like activity and role of secondary bacterial infection in the pathogenesis of trypanosomosis, infected mice were treated with the antibiotic ciprofloxacin. plasma endotoxin-like activity levels, ... | 2009 | 19527451 |
| bidirectional silencing of rna polymerase i transcription by a strand switch region in trypanosoma brucei. | the procyclin genes in trypanosoma brucei are transcribed by rna polymerase i as part of 5-10 kb long polycistronic transcription units on chromosomes vi and x. each procyclin locus begins with two procyclin genes followed by at least one procyclin-associated gene (pag). in procyclic (insect midgut) form trypanosomes, pag mrna levels are about 100-fold lower than those of procyclins. we show that deletion of pag1, pag2 or pag3 results in increased mrna levels from downstream genes in the same tr ... | 2009 | 19531741 |
| antitrypanosomal activity of polycarpol from piptostigma preussi (annonaceae). | polycarpol, sitosterol and sitosterol-3-o-beta-d-glucoside isolated for the first time from piptostigma preussi (annonaceae) occur regularly in some annonaceae such as piptostigma genus. polycarpol exhibits interesting antitrypanosomal activity with an ed(50) value of 5.11 microm on trypanosoma brucei cells. moreover, it inhibits t. brucei glycolytic enzymes gapdh and pfk with ic(50) values of 650 and 180 microm respectively. | 2009 | 19535022 |
| evidence for a degradosome-like complex in the mitochondria of trypanosoma brucei. | mitochondrial rna turnover in yeast involves the degradosome, composed of dss-1 exoribonuclease and suv3 rna helicase. here, we describe a degradosome-like complex, containing suv3 and dss-1 homologues, in the early branching protozoan, trypanosoma brucei. tbsuv3 is mitochondrially localized and co-sediments with tbdss-1 on glycerol gradients. co-immunoprecipitation demonstrates that tbsuv3 and tbdss-1 associate in a stable complex, which differs from the yeast degradosome in that it is not stab ... | 2009 | 19540236 |
| identification of the hit-45 protein from trypanosoma brucei as an fhit protein/dinucleoside triphosphatase: substrate specificity studies on the recombinant and endogenous proteins. | a new member of the fhit protein family, designated hit-45, has been identified in the african trypanosome trypanosoma brucei. recombinant hit-45 proteins were purified from trypanosomal and bacterial protein expression systems and analyzed for substrate specificity using various dinucleoside polyphosphates, including those that contain the 5'-mrna cap, i.e., m(7)gmp. this enzyme exhibited typical dinucleoside triphosphatase activity (ec 3.6.1.29), having its highest specificity for diadenosine ... | 2009 | 19541768 |
| adaptations in the glucose metabolism of procyclic trypanosoma brucei isolates from tsetse flies and during differentiation of bloodstream forms. | procyclic forms of trypanosoma brucei isolated from the midguts of infected tsetse flies, or freshly transformed from a strain that is close to field isolates, do not use a complete krebs cycle. furthermore, short stumpy bloodstream forms produce acetate and are apparently metabolically preadapted to adequate functioning in the tsetse fly. | 2009 | 19542311 |
| special sm core complex functions in assembly of the u2 small nuclear ribonucleoprotein of trypanosoma brucei. | the processing of polycistronic pre-mrnas in trypanosomes requires the spliceosomal small ribonucleoprotein complexes (snrnps) u1, u2, u4/u6, u5, and sl, each of which contains a core of seven sm proteins. recently we reported the first evidence for a core variation in spliceosomal snrnps; specifically, in the trypanosome u2 snrnp, two of the canonical sm proteins, smb and smd3, are replaced by two u2-specific sm proteins, sm15k and sm16.5k. here we identify the u2-specific, nuclear-localized u2 ... | 2009 | 19542313 |
| the trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target. | sphingolipids are important components of eukaryotic membranes, particularly the plasma membrane, and are involved in a diverse array of signal transduction processes. in the eukaryota the biosynthetic pathway for the formation of these lipid species is largely conserved. however, in contrast to mammals which produce sphingomyelin (sm), several pathogenic fungi and protozoa synthesize inositol phosphorylceramide (ipc) as the primary phosphosphingolipid. this process is catalyzed by the enzyme ip ... | 2009 | 19545591 |
| antigenic variation: extending the reach of telomeric silencing. | immune evasion in the parasitic african trypanosome relies upon the silencing of variant surface glycoprotein genes that are found adjacent to telomeres. work on the rap1 telomere-binding protein now indicates that silencing spreads over a sufficient distance to repress these genes. | 2009 | 19549499 |
| the ethanolamine branch of the kennedy pathway is essential in the bloodstream form of trypanosoma brucei. | phosphatidylethanolamine (gpetn), a major phospholipid component of trypanosome membranes, is synthesized de novo from ethanolamine through the kennedy pathway. here the composition of the gpetn molecular species in the bloodstream form of trypanosoma brucei is determined, along with new insights into phospholipid metabolism, by in vitro and in vivo characterization of a key enzyme of the kennedy pathway, the cytosolic ethanolamine-phosphate cytidylyltransferase (tbect). gene knockout indicates ... | 2009 | 19555461 |
| molecular epidemiology of african sleeping sickness. | human sleeping sickness in africa, caused by trypanosoma brucei spp. raises a number of questions. despite the widespread distribution of the tsetse vectors and animal trypanosomiasis, human disease is only found in discrete foci which periodically give rise to epidemics followed by periods of endemicity a key to unravelling this puzzle is a detailed knowledge of the aetiological agents responsible for different patterns of disease--knowledge that is difficult to achieve using traditional micros ... | 2009 | 19555522 |
| activity of indenoisoquinolines against african trypanosomes. | african trypanosomiasis (sleeping sickness), caused by protozoan trypanosoma brucei species, is a debilitating disease that is lethal if untreated. available drugs are antiquated, toxic, and compromised by emerging resistance. the indenoisoquinolines are a class of noncamptothecin topoisomerase ib poisons that are under development as anticancer agents. we tested a variety of indenoisoquinolines for their ability to kill t. brucei. indenoisoquinolines proved trypanocidal at submicromolar concent ... | 2009 | 18824603 |