Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| 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 |
| neuropeptides kill african trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death. | trypanosoma brucei is the causative agent of african sleeping sickness. available treatments are ineffective, toxic and susceptible to resistance by the parasite. here we show that various endogenous neuropeptides act as potent antitrypanosome agents. neuropeptides exerted their trypanolytic activity through an unusual mechanism that involves peptide uptake by the parasite, disruption of lysosome integrity and cytosolic accumulation of glycolytic enzymes. this promotes an energetic metabolism fa ... | 2009 | 19057622 |
| standard culture medium allows clonal dilution of trypanosoma brucei procyclic cells after auto-conditioning. | trypanosoma brucei can be cultured in vitro in the mammalian bloodstream form or in the procyclic (pc) form found in the insect vector. bloodstream trypanosomes can be cloned by limiting dilution, but pcs can only be diluted in conditioned medium, i.e., medium in which pc cells have previously been grown. it is shown here that this limitation does not apply to the most commonly used pc cell strain, lister 427, if free radicals are removed from the medium. the reported benefit of conditioning med ... | 2009 | 19059438 |
| cell morphogenesis of trypanosoma brucei requires the paralogous, differentially expressed calpain-related proteins cap5.5 and cap5.5v. | proteins from the calpain super-family are involved in developmentally- and environmentally-regulated re-modelling of the eukaryotic cytoskeleton and the dynamic organisation of signal transduction cascades. in trypanosomatid parasites, calpain-related gene families are unusually large, but we have little insight into the functional roles played by these molecules during trypanosomatid lifecycles. here we report that cap5.5, a cytoskeletal calpain-related protein subject to strict stage-specific ... | 2009 | 19656721 |
| structure of the c-terminal domain of transcription factor iib from trypanosoma brucei. | in trypanosomes, the production of mrna relies on the synthesis of the spliced leader (sl) rna. expression of the sl rna is initiated at the only known rna polymerase ii promoter in these parasites. in the pathogenic trypanosome, trypanosoma brucei, transcription factor iib (ttfiib) is essential for sl rna gene transcription and cell viability, but has a highly divergent primary sequence in comparison to tfiib in well-studied eukaryotes. here we describe the 2.3 a resolution structure of the c-t ... | 2009 | 19666603 |
| trypanosomatid genomes contain several subfamilies of ingi-related retroposons. | retroposons are ubiquitous transposable elements found in the genomes of most eukaryotes, including trypanosomatids. the african and american trypanosomes (trypanosoma brucei and trypanosoma cruzi) contain long autonomous retroposons of the ingi clade (tbingi and l1tc, respectively) and short nonautonomous truncated versions (tbrime and nartc, respectively), as well as degenerate ingi-related retroposons devoid of coding capacity (dires). in contrast, leishmania major contains only remnants of e ... | 2009 | 19666780 |
| trypanosoma brucei: a putative rna polymerase ii promoter. | rna polymerase ii (pol ii) promoters are rare in the african trypanosome trypanosoma brucei because gene regulation in the parasite is complex and polycistronic. here, we describe a putative pol ii promoter and its structure-function relationship. the promoter has features of an archetypal eukaryotic pol ii promoter including putative canonical ccaat and tata boxes, and an initiator element. however, the spatial arrangement of these elements is only similar to yeast pol ii promoters. deletion ma ... | 2009 | 19703444 |
| immunolocalization and challenge studies using a recombinant vibrio cholerae ghost expressing trypanosoma brucei ca(2+) atpase (tbca2) antigen. | human african trypanosomiasis is a neglected disease caused by trypanosoma brucei spp. a parasite cation pump (ca(2+) atpase; tbca2) essential for survival and cation homeostasis was identified and characterized. it was hypothesized that targeting this pump using a vibrio cholerae ghost (vcg)-based vaccine could protect against murine t. brucei infection. mrna and protein expression of tbca2 was differentially expressed in blood and insect stages of parasites and immunolocalized in the pericellu ... | 2009 | 19706905 |
| nutritional stress affects the tsetse fly's immune gene expression. | tsetse-transmitted trypanosomiasis poses a serious threat to human and animal health in sub-saharan africa. the majority of tsetse flies (glossina spp.) in a natural population will not develop a mature infection of either trypanosoma congolense or trypanosoma brucei sp. because of refractoriness, a phenomenon that is affected by different factors, including the tsetse fly's immune defence. starvation of tsetse flies significantly increases their susceptibility to the establishment of a trypanos ... | 2009 | 19712150 |
| trypanosoma brucei puf9 regulates mrnas for proteins involved in replicative processes over the cell cycle. | many genes that are required at specific points in the cell cycle exhibit cell cycle-dependent expression. in the early-diverging model eukaryote and important human pathogen trypanosoma brucei, regulation of gene expression in the cell cycle and other processes is almost entirely post-transcriptional. here, we show that the t. brucei rna-binding protein puf9 stabilizes certain transcripts during s-phase. target transcripts of puf9--ligka, pnt1 and pnt2--were identified by affinity purification ... | 2009 | 19714224 |
| unraveling the secrets of regulating mitochondrial dna replication. | in this issue, liu et al. (2009) report that maxicircle dna copy number in trypanosomes is regulated by proteolysis of a helicase; the complex kinetoplast dna system yields a clear view of how mitochondrial dna replication can be regulated. | 2009 | 19716784 |
| the selenoproteome is dispensable in bloodstream forms of trypanosoma brucei. | here we show that absence of sep-trna:sec-trna synthase (sepsecs) a key enzyme required for the synthesis of the three trypanosomal selenoproteins does not affect growth of bloodstream forms of trypanosoma brucei. both life cycle stages of t. brucei are highly sensitive to auranofin, a compound known to target selenoproteins. however, the same sensitivity is observed in the sepsecs double knockout cell lines indicating that the trypanocidal action of auranofin is not connected to selenoproteins. ... | 2009 | 19723543 |
| trypanosome glycosylphosphatidylinositol biosynthesis. | trypanosoma brucei, a protozoan parasite, causes sleeping sickness in humans and nagana disease in domestic animals in central africa. the trypanosome surface is extensively covered by glycosylphosphatidylinositol (gpi)-anchored proteins known as variant surface glycoproteins and procyclins. gpi anchoring is suggested to be important for trypanosome survival and establishment of infection. trypanosomes are not only pathogenically important, but also constitute a useful model for elucidating the ... | 2009 | 19724691 |
| synthesis and sar of alkanediamide-linked bisbenzamidines with anti-trypanosomal and anti-pneumocystis activity. | a series of alkanediamide-linked bisbenzamidines was synthesized and tested in vitro against a drug-sensitive strain of trypanosoma brucei brucei, a drug-resistant strain of trypanosoma brucei rhodesiense and pneumocystiscarinii. bisbenzamidines linked with longer alkanediamide chains were potent inhibitors of both strains of t. brucei. however, bisbenzamidines linked with shorter alkanediamide chains were the most potent compounds against p. carinii. n,n'-bis[4-(aminoiminomethyl)phenyl] hexaned ... | 2009 | 19736009 |
| trypanosoma brucei atg8: structural insights into autophagic-like mechanisms in protozoa. | bioinformatic searches of genome databases revealed that the number of autophagy-related genes (atg) is considerably lower in trypanosomes than in higher eukaryotes and even in yeast. this raises the question of whether autophagy in this protozoan parasite is more primitive and represents a rudimentary paradigm due to its early branching off the evolutionary tree. we here present the crystal structure of tbatg8b. this molecule (mw 13.7 kda) belongs to the ubiquitin-like proteins showing the typi ... | 2009 | 19736525 |
| the non-canonical ctd of rnap-ii is essential for productive rna synthesis in trypanosoma brucei. | the carboxy-terminal domain (ctd) of the largest subunit (rpb1) of rna polymerase ii (rnap-ii) is essential for gene expression in metazoa and yeast. the canonical ctd is characterized by heptapeptide repeats. differential phosphorylation of canonical ctd orchestrates transcriptional and co-transcriptional maturation of mrna and snrna. many organisms, including trypanosomes, lack a canonical ctd. in these organisms, the ctd is called a non-canonical ctd or pseudo-ctd (psictd. in the african tryp ... | 2009 | 19742309 |
| genome-wide expression profiling of in vivo-derived bloodstream parasite stages and dynamic analysis of mrna alterations during synchronous differentiation in trypanosoma brucei. | trypanosomes undergo extensive developmental changes during their complex life cycle. crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. these developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. | 2009 | 19747379 |
| the heart of darkness: growth and form of trypanosoma brucei in the tsetse fly. | the first description of african trypanosomes was made over a century ago. the importance of the tsetse in transmission and cyclic development of trypanosomes was discovered soon afterwards, and has been the focus of numerous studies since. however, investigation of trypanosomes in tsetse flies requires high resource investment and unusual patience; hence, many facets of trypanosome biology in the tsetse remain to be characterised despite the long history of research. here, current knowledge and ... | 2009 | 19747880 |
| the aurora kinase in trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation. | aurora b kinase is an essential regulator of chromosome segregation with the action well characterized in eukaryotes. it is also implicated in cytokinesis, but the detailed mechanism remains less clear, partly due to the difficulty in separating the latter from the former function in a growing cell. a chemical genetic approach with an inhibitor of the enzyme added to a synchronized cell population at different stages of the cell cycle would probably solve this problem. in the deeply branched par ... | 2009 | 19750216 |
| streamlined architecture and glycosylphosphatidylinositol-dependent trafficking in the early secretory pathway of african trypanosomes. | the variant surface glycoprotein (vsg) of bloodstream form trypanosoma brucei (tb) is a critical virulence factor. the vsg glycosylphosphatidylinositol (gpi)-anchor strongly influences passage through the early secretory pathway. using a dominant-negative mutation of tbsar1, we show that endoplasmic reticulum (er) exit of secretory cargo in trypanosomes is dependent on the coat protein complex ii (copii) machinery. trypanosomes have two orthologues each of the sec23 and sec24 copii subunits, whi ... | 2009 | 19759175 |
| pssa-2, a membrane-spanning phosphoprotein of trypanosoma brucei, is required for efficient maturation of infection. | the coat of trypanosoma brucei consists mainly of glycosylphosphatidylinositol-anchored proteins that are present in several million copies and are characteristic of defined stages of the life cycle. while these major components of the coats of bloodstream forms and procyclic (insect midgut) forms are well characterised, very little is known about less abundant stage-regulated surface proteins and their roles in infection and transmission. by creating epitope-tagged versions of procyclic-specifi ... | 2009 | 19759911 |
| three redox states of trypanosoma brucei alternative oxidase identified by infrared spectroscopy and electrochemistry. | electrochemistry coupled with fourier transform infrared (ir) spectroscopy was used to investigate the redox properties of recombinant alternative ubiquinol oxidase from trypanosoma brucei, the organism responsible for african sleeping sickness. stepwise reduction of the fully oxidized resting state of recombinant alternative ubiquinol oxidase revealed two distinct ir redox difference spectra. the first of these, signal 1, titrates in the reductive direction as an n = 2 nernstian component with ... | 2009 | 19767647 |
| structure-guided development of selective tbcatb inhibitors. | the trypanosomal cathepsin tbcatb is essential for parasite survival and is an attractive therapeutic target. herein we report the structure-guided development of tbcatb inhibitors with specificity relative to rhodesain and human cathepsins b and l. inhibitors were tested for enzymatic activity, trypanocidal activity, and general cytotoxicity. these data chemically validate tbcatb as a drug target and demonstrate that it is possible to potently and selectively inhibit tbcatb relative to trypanos ... | 2009 | 19769357 |
| crk9 contributes to regulation of mitosis and cytokinesis in the procyclic form of trypanosoma brucei. | the trypanosoma brucei cell cycle is regulated by combinations of cyclin/crks (cdc2 related kinases). recently, two additional cyclins (cyc10, cyc11) and six new crk (crk7-12) homologues were identified in the t. brucei genome database 12. | 2009 | 19772588 |
| novel non-peptidic vinylsulfones targeting the s2 and s3 subsites of parasite cysteine proteases. | we describe here the identification of non-peptidic vinylsulfones that inhibit parasite cysteine proteases in vitro and inhibit the growth of trypanosoma brucei brucei parasites in culture. a high resolution (1.75 a) co-crystal structure of 8a bound to cruzain reveals how the non-peptidic p2/p3 moiety in such analogs bind the s2 and s3 subsites of the protease, effectively recapitulating important binding interactions present in more traditional peptide-based protease inhibitors and natural subs ... | 2009 | 19773167 |
| tbpif5 is a trypanosoma brucei mitochondrial dna helicase involved in processing of minicircle okazaki fragments. | trypanosoma brucei's mitochondrial genome, kinetoplast dna (kdna), is a giant network of catenated dna rings. the network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles. here we report that tbpif5, one of t. brucei's six mitochondrial proteins related to saccharomyces cerevisiae mitochondrial dna helicase scpif1, is involved in minicircle lagging strand synthesis. like its yeast homolog, tbpif5 is a 5' to 3' dna helicase. together with other enzymes thought to be ... | 2009 | 19779567 |
| lipopolysaccharide binding protein in the acute phase response of experimental murine trypanosoma brucei brucei infection. | cellular responses to lipopolysaccharide (lps) are enhanced by lps-binding protein (lbp). the present study investigated the acute phase response of lbp during trypanosoma brucei brucei infection in mice. mean plasma concentrations of lbp increased two-fold by the seventh day following infection, but decreased to intermediate levels by the 14th day. there were no significant differences in lbp concentrations of infected/antibiotic-treated and infected/untreated mice. at 35 days post-infection, t ... | 2009 | 19022463 |
| trypanosoma brucei brucei: effects of ferrous iron and heme on ecto-nucleoside triphosphate diphosphohydrolase activity. | trypanosoma brucei brucei is the causative agent of animal african trypanosomiasis, also called nagana. procyclic vector form resides in the midgut of the tsetse fly, which feeds exclusively on blood. hemoglobin digestion occurs in the midgut resulting in an intense release of free heme. in the present study we show that the magnesium-dependent ecto-nucleoside triphosphate diphosphohydrolase (e-ntpdase) activity of procyclic t. brucei brucei is inhibited by ferrous iron and heme. the inhibition ... | 2009 | 19027737 |
| trypanosome spliced-leader-associated rna (sla1) localization and implications for spliced-leader rna biogenesis. | spliced-leader-associated rna (sla1) guides the pseudouridylation at position -12 (relative to the 5' splice site) of the spliced-leader (sl) rna in all trypanosomatid species. nevertheless, the exact role of this rna is currently unknown. here, we demonstrate that the absence of pseudouridine on leptomonas collosoma sl rna has only a minor effect on the ability of this rna to function in trans splicing in vivo. to investigate the possible role of sla1 during sl rna biogenesis, the structure of ... | 2009 | 19028994 |
| identification of a glycosylphosphatidylinositol anchor-modifying beta1-3 n-acetylglucosaminyl transferase in trypanosoma brucei. | trypanosoma brucei expresses complex glycoproteins throughout its life cycle. a review of its repertoire of glycosidic linkages suggests a minimum of 38 glycosyltransferase activities. of these, five have been experimentally related to specific genes and a further nine can be associated with candidate genes. the remaining linkages have no obvious candidate glycosyltransferase genes; however, the t. brucei genome contains a family of 21 putative udp sugar-dependent glycosyltransferases of unknown ... | 2009 | 19040631 |
| functional studies of an evolutionarily conserved, cytochrome b5 domain protein reveal a specific role in axonemal organisation and the general phenomenon of post-division axonemal growth in trypanosomes. | eukaryotic cilia and flagella are highly conserved structures composed of a canonical 9+2 microtubule axoneme. several recent proteomic studies of cilia and flagella have been published, including a proteome of the flagellum of the protozoan parasite trypanosoma brucei. comparing proteomes reveals many novel proteins that appear to be widely conserved in evolution. amongst these, we found a previously uncharacterised protein which localised to the axoneme in t. brucei, and therefore named it try ... | 2009 | 19009637 |
| synthesis and antiparasitic and antifungal evaluation of 2'-arylsubstituted-1h,1'h-[2,5']bisbenzimidazolyl-5-carboxamidines. | a series of 2'-arylsubstituted-1h,1'h-[2,5']-bisbenzimidazolyl-5-carboxamidines were prepared in a six-step process starting from 4-amino-3-nitrobenzonitrile. the antiparasitic activity against trypanosoma brucei rhodesiense (t.b.r.), plasmodium falciparum (p.f.), leishmania donovani (l.d.) and trypanosoma cruzi (t.c.) and antifungal activity against candida albicans and candida krusei were evaluated in vitro. several compounds showed promising in vitro activity against t.b.r., p.f. and c. albic ... | 2009 | 19010569 |
| trypanosomes have six mitochondrial dna helicases with one controlling kinetoplast maxicircle replication. | kinetoplast dna (kdna), the trypanosome mitochondrial dna, contains thousands of minicircles and dozens of maxicircles interlocked in a giant network. remarkably, trypanosoma brucei's genome encodes 8 pif1-like helicases, 6 of which are mitochondrial. we now show that tbpif2 is essential for maxicircle replication. maxicircle abundance is controlled by tbpif2 level, as rnai of this helicase caused maxicircle loss, and its overexpression caused a 3- to 6-fold increase in maxicircle abundance. thi ... | 2009 | 19646907 |
| trypanosoma brucei amp-activated kinase subunit homologs influence surface molecule expression. | the african trypanosome, trypanosoma brucei, can gauge its environment by sensing nutrient availability. for example, procyclic form (pf) trypanosomes monitor changes in glucose levels to regulate surface molecule expression, which is important for survival in the tsetse fly vector. the molecular connection between glycolysis and surface molecule expression is unknown. here we partially characterize t. brucei homologs of the beta and gamma subunits of the amp-activated protein kinase (ampk), and ... | 2009 | 19647733 |
| quantitative differences in immune responses in mouse strains that differ in their susceptibility to trypanosoma brucei brucei infection. | we compared the relative resistance and soluble variant surface glycoprotein (vsg)-specific responses in (c57bl/6 x balb/c)-f1 (b6b-f1) and c3h mice during infection with trypanosoma brucei brucei, the hemoprotozoan parasite causing a debilitating disease in man and livestock. we demonstrated that c3h mice are relatively more trypanosusceptible, as evidenced by their reduced ability to control parasitemia and shorter survival time, than b6b-f1 mice. quantitative differences in the pattern of cyt ... | 2009 | 19652484 |
| genome-wide computational identification of functional rna elements in trypanosoma brucei. | post-transcriptional regulation of gene expression is the dominant regulatory mechanism in trypanosomatids as their mrnas are transcribed from polycistronic units. a few cis-acting rna elements in 3'-untranslated regions of mrnas have been identified in trypanosomatids, which affect the mrna stability or translation rate in different life stages of these parasites. other functional rnas (frnas) also play essential roles in these organisms. however, there has been no genome-wide analysis for iden ... | 2009 | 19653906 |
| improved tricyclic inhibitors of trypanothione reductase by screening and chemical synthesis. | trypanothione reductase (tryr) is a key validated enzyme in the trypanothione-based redox metabolism of pathogenic trypanosomes and leishmania parasites. this system is absent in humans, being replaced with glutathione and glutathione reductase, and as such offers a target for selective inhibition. as part of a program to discover antiparasitic drugs, the lopac1280 library of 1266 compounds was screened against tryr and the top hits evaluated against glutathione reductase and t. brucei parasites ... | 2009 | 19557801 |
| synthesis and evaluation of 1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)piperidine (btcp) analogues as inhibitors of trypanothione reductase. | thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (tryr), a potential drug target in trypanosome and leishmania parasites. the lead compound btcp (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (k(i)=1 microm) and biologically active against bloodstream t. brucei (ec(50)=10 microm), but with poor selectivity against mammalian mrc5 cells (ec(50)=29 microm). analogues with improved ... | 2009 | 19557802 |
| dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in trypanosoma brucei using chemical and genetic methods. | the bifunctional trypanothione synthetase-amidase (trys) comprises two structurally distinct catalytic domains for synthesis and hydrolysis of trypanothione (n(1),n(8)-bis(glutathionyl)spermidine). this unique dithiol plays a pivotal role in thiol-redox homeostasis and in defence against chemical and oxidative stress in trypanosomatids. a tetracycline-dependent conditional double knockout of trys (cdko) was generated in bloodstream trypanosoma brucei. culture of cdko parasites without tetracycli ... | 2009 | 19558432 |
| human innate immunity against african trypanosomes. | humans are naturally resistant to infection by the african trypanosome prototype trypanosoma brucei brucei, and only two variant clones of this parasite can avoid this innate immunity and cause sleeping sickness. the resistance to t. brucei is due to serum complexes associating apolipoprotein a-1 (apoa1) with two primate-specific proteins, apolipoprotein l-1 (apol1) and haptoglobin-related protein (hpr). we discuss recent advances on the respective functions of apol1 and hpr in this system. apol ... | 2009 | 19559585 |
| endotoxin-like effects in acute phase response to trypanosoma brucei brucei infection are not due to gastrointestinal leakage. | trypanosomosis is mainly an immunological and inflammatory response mediated by increased levels of pro-inflammatory cytokines. evidence suggests that pathological changes produced during infection with trypanosomes could be initiated by nonspecific endotoxin-like substances in trypanosomes and/or gram-negative secondary bacterial infection. studies in trypanosome-infected rats indicate damage to the gastrointestinal tract (git) accompanied by increased leakage of the git mucosa. the current stu ... | 2009 | 19567273 |
| thiolation controls cytoplasmic trna stability and acts as a negative determinant for trna editing in mitochondria. | kinetoplastids encode a single nuclear tryptophanyl trna that contains a cca anticodon able to decode the ugg codons used in cytoplasmic protein synthesis but cannot decode the mitochondrial uga codons. following mitochondrial import, this problem is circumvented in trypanosoma brucei by specifically editing the trna(trp) anticodon to uca, which can now decode the predominant mitochondrial uga tryptophan codons. this trna also undergoes an unusual thiolation at position 33 of the anticodon loop, ... | 2009 | 19574216 |
| role of ap-1 in developmentally regulated lysosomal trafficking in trypanosoma brucei. | african trypanosomes are the causative agents of human trypanosomiasis (sleeping sickness). the pathogenic stage of the parasite has unique adaptations to life in the bloodstream of the mammalian host, including upregulation of endocytic and lysosomal activities. we investigated stage-specific requirements for cytoplasmic adaptor/clathrin machinery in post-golgi apparatus biosynthetic sorting to the lysosome using rna interference silencing of the tbmu1 subunit of adaptor complex 1 (ap-1), in co ... | 2009 | 19581441 |
| trans-sialidase from trypanosoma brucei as a potential target for dna vaccine development against african trypanosomiasis. | african trypanosomiasis (at), also known as sleeping sickness in humans and nagana in animals, is a disease caused by the protozoan parasite trypanosoma brucei. at is an extremely debilitating disease in human, cattle, and wild animals, and the treatment is difficult with frequent relapses. this work shows that balb-c mice immunized intramuscularly with a single dose (100 microg) of a plasmid dna encoding the 5'-terminal region of the trans-sialidase (ntsa) gene of t. brucei brucei are able to p ... | 2009 | 19582478 |
| structural effects of a dimer interface mutation on catalytic activity of triosephosphate isomerase. the role of conserved residues and complementary mutations. | the active site of triosephosphate isomerase (tim, ec: 5.3.1.1), a dimeric enzyme, lies very close to the subunit interface. attempts to engineer monomeric enzymes have yielded well-folded proteins with dramatically reduced activity. the role of dimer interface residues in the stability and activity of the plasmodium falciparum enzyme, pftim, has been probed by analysis of mutational effects at residue 74. the pftim triple mutant w11f/w168f/y74w (y74w*) has been shown to dissociate at low protei ... | 2009 | 19583769 |
| characteristics of novel insect defensin-based membrane-disrupting trypanocidal peptides. | synthetic d- and l-amino acid type cationic 9-mer peptides (all sequences were synthesized as d- or l-amino acids) derived from the active sites of insect defensins were tested for their ability to modify the growth of blood-stream form african trypanosomes in vitro. one of them, the d-type peptide a (rlylrigrr-nh(2)), irreversibly suppressed proliferation of the trypanosoma brucei brucei gutat3.1 parasite. the presence of negatively charged phosphatidylserine on the surface of the parasites was ... | 2009 | 19584534 |
| diversity oriented syntheses of fused pyrimidines designed as potential antifolates. | diversity oriented syntheses of some furo[2,3-d]pyrimidines and pyrrolo[2,3-d]pyrimidines related to folate, guanine, and diaminopyrimidine-containing drugs have been developed for the preparation of potential anti-infective and anticancer compounds. amide couplings and suzuki couplings on the basic heterocyclic templates were used, in the latter case yields being especially high using aromatic trifluoroborates as the coupling partner. a new ring synthesis of 6-aryl-substituted deazaguanines bea ... | 2009 | 19590778 |
| smn-assisted assembly of snrnp-specific sm cores in trypanosomes. | spliceosomal small nuclear ribonucleoproteins (snrnps) in trypanosomes contain either the canonical heptameric sm ring (u1, u5, spliced leader snrnps), or variant sm cores with snrna-specific sm subunits (u2, u4 snrnps). searching for specificity factors, we identified smn and gemin2 proteins that are highly divergent from known orthologs. smn is splicing-essential in trypanosomes and nuclear-localized, suggesting that sm core assembly in trypanosomes is nuclear. we demonstrate in vitro that smn ... | 2009 | 19605687 |
| the trypanocidal effect of no-releasing agents is not due to inhibition of the major cysteine proteinase in trypanosoma brucei. | the lysosomal cysteine proteinase activity of bloodstream forms of trypanosoma brucei is a validated drug target. previously, it was reported that nitric oxide (no)-releasing agents inhibit the catalytic activity of cysteine proteinases of the protozoan parasites leishmania infantum, trypanosoma cruzi and plasmodium falciparum. in this study, we investigated the effect of the no-donors s-nitrosoglutathione, (+/-)-(e)-4-ethyl-2[(e)-hydroxyimino]-5-nitro-3-hexenamide, 3-morpholinosydnonimine (sin- ... | 2009 | 19609563 |
| downregulation of mitochondrial porin inhibits cell growth and alters respiratory phenotype in trypanosoma brucei. | porin is the most abundant outer membrane (om) protein of mitochondria. it forms the aqueous channel on the mitochondrial om and mediates major metabolite flux between mitochondria and cytosol. mitochondrial porin in trypanosoma brucei, a unicellular parasitic protozoan and the causative agent of african trypanosomiasis, possesses a beta-barrel structure similar to the bacterial om porin ompa. t. brucei porin (tbporin) is present as a monomer as well as an oligomer on the mitochondrial om, and i ... | 2009 | 19617393 |
| specific detection and identification of african trypanosomes in bovine peripheral blood by means of a pcr-elisa assay. | the aim of the present study was to develop a pcr-elisa assay for the detection and differentiation of the main african pathogen trypanosomal species present in peripheral blood of cattle. the proposed methodology allows to specifically differentiate trypanosoma congolense, trypanosoma vivax and the subgenus trypanozoon, by means of a sensitive universal pcr amplifying trypanosome dna followed by an elisa-based hybridization with three highly specific probes. the semi-nested pcr had a sensitivit ... | 2009 | 19619947 |
| distinct and overlapping functions of mrp1/2 and rbp16 in mitochondrial rna metabolism. | mitochondrial rna metabolism in trypanosoma brucei is a complex process involving both extensive rna editing and control of rna stability. mrp1/2 and rbp16 are two factors that have been implicated in regulating the editing and stability of specific mrnas. these two factors exhibit similar nonspecific rna binding and rna-annealing activities, suggesting that some of their actions may have been previously masked by functional redundancy. here, we examine the functional interaction of mrp1/2 and r ... | 2009 | 19620277 |
| new treatment option for second-stage african sleeping sickness: in vitro and in vivo efficacy of aza analogs of db289. | african sleeping sickness is a fatal parasitic disease, and all drugs currently in use for treatment have strong liabilities. it is essential to find new, effective, and less toxic drugs, ideally with oral application, to control the disease. in this study, the aromatic diamidine db75 (furamidine) and two aza analogs, db820 and db829 (cpd-0801), as well as their methoxyamidine prodrugs and amidoxime metabolites, were evaluated against african trypanosomes. the active parent diamidines showed sim ... | 2009 | 19620327 |
| vinyl sulfones as antiparasitic agents and a structural basis for drug design. | cysteine proteases of the papain superfamily are implicated in a number of cellular processes and are important virulence factors in the pathogenesis of parasitic disease. these enzymes have therefore emerged as promising targets for antiparasitic drugs. we report the crystal structures of three major parasite cysteine proteases, cruzain, falcipain-3, and the first reported structure of rhodesain, in complex with a class of potent, small molecule, cysteine protease inhibitors, the vinyl sulfones ... | 2009 | 19620707 |
| bioluminescent imaging of trypanosoma brucei shows preferential testis dissemination which may hamper drug efficacy in sleeping sickness. | monitoring trypanosoma spread using real-time imaging in vivo provides a fast method to evaluate parasite distribution especially in immunoprivileged locations. here, we generated monomorphic and pleomorphic recombinant trypanosoma brucei expressing the renilla luciferase. in vitro luciferase activity measurements confirmed the uptake of the coelenterazine substrate by live parasites and light emission. we further validated the use of renilla luciferase-tagged trypanosomes for real-time biolumin ... | 2009 | 19621071 |
| acetate produced in the mitochondrion is the essential precursor for lipid biosynthesis in procyclic trypanosomes. | acetyl-coa produced in mitochondria from carbohydrate or amino acid catabolism needs to reach the cytosol to initiate de novo synthesis of fatty acids. all eukaryotes analyzed so far use a citrate/malate shuttle to transfer acetyl group equivalents from the mitochondrial matrix to the cytosol. here we investigate how this acetyl group transfer occurs in the procyclic life cycle stage of trypanosoma brucei, a protozoan parasite responsible of human sleeping sickness and economically important liv ... | 2009 | 19625628 |
| distinct donor and acceptor specificities of trypanosoma brucei oligosaccharyltransferases. | asparagine-linked glycosylation is catalysed by oligosaccharyltransferase (otase). in trypanosoma brucei otase activity is catalysed by single-subunit enzymes encoded by three paralogous genes of which tbstt3b and tbstt3c can complement a yeast deltastt3 mutant. the two enzymes have overlapping but distinct peptide acceptor specificities, with tbstt3c displaying an enhanced ability to glycosylate sites flanked by acidic residues. tbstt3a and tbstt3b, but not tbstt3c, are transcribed in the blood ... | 2009 | 19629045 |
| what has dna sequencing revealed about the vsg expression sites of african trypanosomes? | antigenic variation is crucial for the survival of african trypanosomes in mammals and involves switches in expression of variant surface glycoprotein genes, which are co-transcribed with a number of expression-site-associated genes (esags) from loci termed 'bloodstream expression sites' (bess). trypanosomes possess multiple bess, although the reason for this (and why esags are resident in these loci) has remained a subject of debate. the genome sequence of trypanosoma brucei, released in 2005, ... | 2009 | 19632154 |
| fate of glycosylphosphatidylinositol (gpi)-less procyclin and characterization of sialylated non-gpi-anchored surface coat molecules of procyclic-form trypanosoma brucei. | a trypanosoma brucei tbgpi12 null mutant that is unable to express cell surface procyclins and free glycosylphosphatidylinositols (gpi) revealed that these are not the only surface coat molecules of the procyclic life cycle stage. here, we show that non-gpi-anchored procyclins are n-glycosylated, accumulate in the lysosome, and appear as proteolytic fragments in the medium. we also show, using lectin agglutination and galactose oxidase-nab(3)h(4) labeling, that the cell surface of the tbgpi12 nu ... | 2009 | 19633269 |
| cohesin regulates vsg monoallelic expression in trypanosomes. | antigenic variation allows trypanosoma brucei to evade the host immune response by switching the expression of 1 out of approximately 15 telomeric variant surface glycoprotein (vsg) expression sites (ess). vsg es transcription is mediated by rna polymerase i in a discrete nuclear site named the es body (esb). however, nothing is known about how the monoallelic vsg es transcriptional state is maintained over generations. in this study, we show that during s and g2 phases and early mitosis, the ac ... | 2009 | 19635842 |
| comparative histopathology of the lymph nodes, spleen, liver and kidney in experimental ovine trypanosomosis. | the infection of yankassa rams with three important trypanosome species affecting livestock, namely, trypanosoma congolense, t. vivax and t. bruceiproduced both acute and chronic fatal conditions. chronic infections were induced in the three infections by the application of subcurative doses of diaminazene aceturate (berenil). pathological changes in the infected animals included splenomegaly and hepatomegaly which were more pronounced in acute than in chronic t. congolense infection. however, t ... | 2009 | 21344787 |
| in vitro antiprotozoal activity of some xanthones isolated from the roots of andrographis paniculata. | four xanthones isolated from the roots of andrographis paniculata were tested in vitro for antiprotozoal activity against trypanosoma brucei brucei, trypanosoma cruzi and leishmania infantum. compound tdr13011 (1,2-dihydroxy-6,8-dimethoxy-xanthone) showed good activity against t. b. brucei and l. infantum with a 50% inhibitory concentration (ic50) of 4.6 microg/ml and 8 microg/ml respectively. xanthones from the roots of andrographis paniculata exhibited promising anti-protozoal activity and the ... | 2009 | 18683849 |
| crystal structure of phosphoglucose isomerase from trypanosoma brucei complexed with glucose-6-phosphate at 1.6 a resolution. | enzymes of glycolysis in trypanosoma brucei have been identified as potential drug targets for african sleeping sickness because glycolysis is the only source of atp for the bloodstream form of this parasite. several inhibitors were previously reported to bind preferentially to trypanosomal phosphoglucose isomerase (pgi, the second enzyme in glycolysis) than to mammalian pgis, which suggests that pgi might make a good target for species-specific drug design. herein, we report recombinant express ... | 2009 | 18561188 |
| 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 |
| glycosylphosphatidylinositol-specific phospholipase c regulates transferrin endocytosis in the african trypanosome. | gpi-plc (glycosylphosphatidylinositol-specific phospholipase c) is expressed in bloodstream-form trypanosoma brucei, a protozoan that causes human african trypanosomiasis. loss of genes encoding gpi-plc reduces the virulence of a pleomorphic strain of the parasite, for reasons that are not clear. in the present paper, we report that gpi-plc stimulates endocytosis of transferrin by 300-500%. surprisingly, gpi-plc is not detected at endosomes, suggesting that the enzyme does not interact directly ... | 2009 | 18785878 |
| characterization of a novel obg-like atpase in the protozoan trypanosoma cruzi. | we characterized a gene encoding an ychf-related protein, tcychf, potentially associated with the protein translation machinery of trypanosoma cruzi. ychf belongs to the translation factor-related (trafac) class of p-loop ntpases. the coding region of the gene is 1185bp long and encodes a 44.3kda protein. blastx searches showed tcychf to be very similar (45-86%) to putative gtp-binding proteins from eukaryotes, including some species of trypanosomatids (leishmania major and trypanosoma brucei). ... | 2009 | 18713637 |
| a kinetoplastid brca2 interacts with dna replication protein cdc45. | the gene brca2, first identified as a breast cancer susceptibility locus in humans, encodes a protein involved in dna repair in mammalian cells and mutations in this gene confer increased risk of breast cancer. here we report a functional characterisation of a trypanosoma brucei brca2 (tbbrca2) orthologue and show that the protein interacts directly with tbrad51. a further protein-protein interaction screen using tbbrca2 identified other interacting proteins, including a trypanosome orthologue o ... | 2009 | 18723021 |
| assembly of the trypanosoma brucei 60s ribosomal subunit nuclear export complex requires trypanosome-specific proteins p34 and p37. | we previously identified two trypanosoma brucei rna binding proteins, p34 and p37, and determined that they are essential for proper ribosomal assembly in this organism. loss of these proteins via rna interference is lethal and causes a decrease in both 5s rrna levels and formation of 80s ribosomes, concomitant with a decrease in total cellular protein synthesis. these data suggest that these proteins are involved at some point in the ribosomal biogenesis pathway. in the current study, we have p ... | 2009 | 18723605 |
| proteomic scale high-sensitivity analyses of gpi membrane anchors. | glycosylphosphatidylinositol (gpi) anchored proteins are ubiquitous in eukaryotic cells. earlier analysis methods required large amounts of purified protein to elucidate the structure of the gpi. this paper describes methods for analyzing gpis on a 'proteomic' scale. partially purified proteins may be run on sodium dodecyl sulphate polyacrylamide gel electrophoresis and then blotted onto a polyvinylidene difluoride (pvdf) membrane. following identification of the protein the piece of pvdf may be ... | 2009 | 18330699 |
| antiplasmodial and antitrypanosomal activity of plants from the kingdom of saudi arabia. | the antiplasmodial and antitrypanosomal activity of the methanol extracts of 42 plants collected from the kingdom of saudi arabia and some fractions obtained thereof were evaluated. the antiplasmodial activity was tested in vitro against chloroquine-resistant strain (k1) and sensitive strain (fcr3), and the antitrypanosomal activity was tested in vitro against trypanosoma brucei brucei gutat 3.1 strain. for host cells, the cytotoxicity of the active extracts was also evaluated against the mrc5 h ... | 2009 | 19067114 |