| identification of different trypanosome species in the mid-guts of tsetse flies of the malanga (kimpese) sleeping sickness focus of the democratic republic of congo. | the malanga sleeping sickness focus of the democratic republic of congo has shown an epidemic evolution of disease during the last century. however, following case detection and treatment, the prevalence of the disease decreased considerably. no active survey has been undertaken in this focus for a couple of years. to understand the current epidemiological status of sleeping sickness as well as the animal african trypanosomiasis in the malanga focus, we undertook the identification of tsetse blo ... | 2012 | 22992486 |
| intraflagellar transport proteins cycle between the flagellum and its base. | intraflagellar transport (ift) is necessary for the construction of cilia and flagella. ift proteins are concentrated at the base of the flagellum but little is known about the actual role of this pool of proteins. here, ift was investigated in trypanosoma brucei, an attractive model for flagellum studies, using gfp fusions with ift52 or the ift dynein heavy chain dhc2.1. tracking analysis by a curvelet method allowing automated separation of forward and return transport demonstrated a uniform s ... | 2013 | 22992454 |
| the zinc finger protein tczfp2 binds target mrnas enriched during trypanosoma cruzi metacyclogenesis. | trypanosomes are parasitic protozoa in which gene expression is primarily controlled through the regulation of mrna stability and translation. this post-transcriptional control is mediated by various families of rna-binding proteins, including those with zinc finger ccch motifs. ccch zinc finger proteins have been shown to be essential to differentiation events in trypanosomatid parasites. here, we functionally characterise tczfp2 as a predicted post-transcriptional regulator of differentiation ... | 2012 | 22990970 |
| ¹h, ¹³c and ¹⁵n resonance assignments of tfiis2-1 pwwp domain from trypanosoma brucei. | tfiis2-1, one of the two trypanosome homologues of transcription elongation factor tfiis (tbtfiis1, tbtfiis2-1), with a pwwp domain in the n-terminus, has a possible association with the largest subunit of rna polymerase ii (rpb1) and shares an essential function with tbtfiis1 in the growth of trypanosoma brucei. here we report the resonance assignments of the protein backbone of the pwwp domain of tfiis2-1 from t. brucei. | 2013 | 22987229 |
| identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of hat. | a library of 1,4-benzodiazepines has been synthesised and evaluated for activity against trypanosoma brucei, a causative parasite of human african trypanosomiasis (hat). the most potent of these derivatives has an mic value of 0.97 μm. herein we report the design, synthesis and biological evaluation of the abovementioned compounds. | 2012 | 22985960 |
| map kinase kinase 1 (mkk1) is essential for transmission of trypanosoma brucei by glossina morsitans. | map kinase kinase 1 (mkk1) is encoded by a single copy gene in trypanosoma brucei. it has been shown recently that mkk1 is not essential for bloodstream forms [14]. to investigate the requirement for mkk1 in other life-cycle stages we generated null mutants in procyclic forms of a fly-transmissible strain. these grew normally in culture and were able to establish midgut infections in tsetse at normal rates and intensities, but were incapable of colonising the salivary glands. transformation of n ... | 2012 | 22985893 |
| the essential polysome-associated rna-binding protein rbp42 targets mrnas involved in trypanosoma brucei energy metabolism. | rna-binding proteins that target mrna coding regions are emerging as regulators of post-transcriptional processes in eukaryotes. here we describe a newly identified rna-binding protein, rbp42, which targets the coding region of mrnas in the insect form of the african trypanosome, trypanosoma brucei. rbp42 is an essential protein and associates with polysome-bound mrnas in the cytoplasm. a global survey of rbp42-bound mrnas was performed by applying hits-clip technology, which captures protein-rn ... | 2012 | 22966087 |
| endogenous sterol biosynthesis is important for mitochondrial function and cell morphology in procyclic forms of trypanosoma brucei. | sterol biosynthesis inhibitors are promising entities for the treatment of trypanosomal diseases. insect forms of trypanosoma brucei, the causative agent of sleeping sickness, synthesize ergosterol and other 24-alkylated sterols, yet also incorporate cholesterol from the medium. while sterol function has been investigated by pharmacological manipulation of sterol biosynthesis, molecular mechanisms by which endogenous sterols influence cellular processes remain largely unknown in trypanosomes. he ... | 2012 | 22964455 |
| catechol pyrazolinones as trypanocidals: fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal phosphodiesterase b1. | trypanosomal phosphodiesterases b1 and b2 (tbrpdeb1 and tbrpdeb2) play an important role in the life cycle of trypanosoma brucei, the causative parasite of human african trypanosomiasis (hat), also known as african sleeping sickness. we used homology modeling and docking studies to guide fragment growing into the parasite-specific p-pocket in the enzyme binding site. the resulting catechol pyrazolinones act as potent tbrpdeb1 inhibitors with ic₅₀ values down to 49 nm. the compounds also block pa ... | 2012 | 22963052 |
| telomere length affects the frequency and mechanism of antigenic variation in trypanosoma brucei. | trypanosoma brucei is a master of antigenic variation and immune response evasion. utilizing a genomic repertoire of more than 1000 variant surface glycoprotein-encoding genes (vsgs), t. brucei can change its protein coat by "switching" from the expression of one vsg to another. each active vsg is monoallelically expressed from only one of approximately 15 subtelomeric sites. switching vsg expression occurs by three predominant mechanisms, arguably the most significant of which is the non-recipr ... | 2012 | 22952449 |
| targeting the substrate preference of a type i nitroreductase to develop antitrypanosomal quinone-based prodrugs. | nitroheterocyclic prodrugs are used to treat infections caused by trypanosoma cruzi and trypanosoma brucei. a key component in selectivity involves a specific activation step mediated by a protein homologous with type i nitroreductases, enzymes found predominantly in prokaryotes. using data from determinations based on flavin cofactor, oxygen-insensitive activity, substrate range, and inhibition profiles, we demonstrate that ntrs from t. cruzi and t. brucei display many characteristics of their ... | 2012 | 22948871 |
| stable isotope-assisted metabolomics for network-wide metabolic pathway elucidation. | the combination of high-resolution lc-ms-based untargeted metabolomics with stable isotope tracing provides a global overview of the cellular fate of precursor metabolites. this methodology enables detection of putative metabolites from biological samples and simultaneous quantification of the pattern and extent of isotope labeling. labeling of trypanosoma brucei cell cultures with 50% uniformly (13)c-labeled glucose demonstrated incorporation of glucose-derived carbon into 187 of 588 putatively ... | 2012 | 22946681 |
| cell-cycle-regulated control of vsg expression site silencing by histones and histone chaperones asf1a and caf-1b in trypanosoma brucei. | antigenic variation in african trypanosomes involves monoallelic expression and reversible silencing of variant surface glycoprotein (vsg) genes found adjacent to telomeres in polycistronic expression sites (ess). we assessed the impact on es silencing of five candidate essential chromatin-associated factors that emerged from a genome-wide rna interference viability screen. using this approach, we demonstrate roles in vsg es silencing for two histone chaperones. defects in s-phase progression in ... | 2012 | 22941664 |
| dot1a-dependent h3k76 methylation is required for replication regulation in trypanosoma brucei. | cell-cycle progression requires careful regulation to ensure accurate propagation of genetic material to the daughter cells. although many cell-cycle regulators are evolutionarily conserved in the protozoan parasite trypanosoma brucei, novel regulatory mechanisms seem to have evolved. here, we analyse the function of the histone methyltransferase dot1a during cell-cycle progression. over-expression of dot1a generates a population of cells with aneuploid nuclei as well as enucleated cells. detail ... | 2012 | 22941659 |
| probing why trypanosomes assemble atypical cytochrome c with an axxch haem-binding motif instead of cxxch. | mitochondrial cytochromes c and c1 are core components of the respiratory chain of all oxygen-respiring eukaryotes. these proteins contain haem, covalently bound to the polypeptide in a catalysed post-translational modification. in all eukaryotes, except members of the protist phylum euglenozoa, haem attachment is to the cysteine residues of a cxxch haem-binding motif. in the euglenozoa, which include medically relevant trypanosomatid parasites, haem attachment is to a single cysteine residue in ... | 2012 | 22928879 |
| antitrypanosomal and cysteine protease inhibitory activities of alkyldiamine cryptolepine derivatives. | cryptolepine derivatives containing alkyldiamine side-chains, 2, with potent inhibitory activity against trypanosoma brucei brucei are reported. compounds 2 showed improved activity and selectivity to t. b. brucei when compared to the lead compound. the most selective compound, 2k, presents a selectivity index value of 6200 and an ic(50) of 10nm against the parasite. these derivatives are also potent inhibitors of the trypanosome papain-like cysteine proteases cruzain, which could, at least in p ... | 2012 | 22926067 |
| small interfering rna-producing loci in the ancient parasitic eukaryote trypanosoma brucei. | at the core of the rna interference (rnai) pathway in trypanosoma brucei is a single argonaute protein, tbago1, with an established role in controlling retroposon and repeat transcripts. recent evidence from higher eukaryotes suggests that a variety of genomic sequences with the potential to produce double-stranded rna are sources for small interfering rnas (sirnas). | 2012 | 22925482 |
| stoking the drug target pipeline for human african trypanosomiasis. | trypanosoma brucei is the causative agent of african sleeping sickness, putting at risk up to 50 million people in sub-saharan africa. current drug therapies are limited by toxicity and difficult treatment regimes and as the development of vaccines remains unlikely, the identification of better drugs to control this deadly disease is needed. strategies for the identification of new lead compounds include phenotypic screening or target-based approaches. implementation of the latter has been hampe ... | 2012 | 22925123 |
| mutational analysis of trypanosoma brucei editosome proteins krepb4 and krepb5 reveals domains critical for function. | the transcriptome of kinetoplastid mitochondria undergoes extensive rna editing that inserts and deletes uridine residues (u's) to produce mature mrnas. the editosome is a multiprotein complex that provides endonuclease, tutase, exonuclease, and ligase activities required for rna editing. the editosome's krepb4 and krepb5 proteins are essential for editosome integrity and parasite viability and contain semi-conserved motifs corresponding to zinc finger, rnase iii, and puf domains, but to date no ... | 2012 | 22919050 |
| translocation of solutes and proteins across the glycosomal membrane of trypanosomes; possibilities and limitations for targeting with trypanocidal drugs. | glycosomes are specialized peroxisomes found in all kinetoplastid organisms. the organelles are unique in harbouring most enzymes of the glycolytic pathway. matrix proteins, synthesized in the cytosol, cofactors and metabolites have to be transported across the membrane. recent research on trypanosoma brucei has provided insight into how these translocations across the membrane occur, although many details remain to be elucidated. proteins are imported by a cascade of reactions performed by spec ... | 2013 | 22914253 |
| chemical proteomic analysis reveals the drugability of the kinome of trypanosoma brucei. | the protozoan parasite trypanosoma brucei is the causative agent of african sleeping sickness, and there is an urgent unmet need for improved treatments. parasite protein kinases are attractive drug targets, provided that the host and parasite kinomes are sufficiently divergent to allow specific inhibition to be achieved. current drug discovery efforts are hampered by the fact that comprehensive assay panels for parasite targets have not yet been developed. here, we employ a kinase-focused chemo ... | 2012 | 22908928 |
| third target of rapamycin complex negatively regulates development of quiescence in trypanosoma brucei. | african trypanosomes are protozoan parasites transmitted by a tsetse fly vector to a mammalian host. the life cycle includes highly proliferative forms and quiescent forms, the latter being adapted to host transmission. the signaling pathways controlling the developmental switch between the two forms remain unknown. trypanosoma brucei contains two target of rapamycin (tor) kinases, tbtor1 and tbtor2, and two tor complexes, tbtorc1 and tbtorc2. surprisingly, two additional tor kinases are encoded ... | 2012 | 22908264 |
| explorations of linked editosome domains leading to the discovery of motifs defining conserved pockets in editosome ob-folds. | trypanosomatids form a group of protozoa which contain parasites of human, animals and plants. several of these species cause major human diseases, including trypanosoma brucei which is the causative agent of human african trypanosomiasis, also called sleeping sickness. these organisms have many highly unusual features including a unique u-insertion/deletion rna editing process in the single mitochondrion. a key multi-protein complex, called the ∼20s editosome, or editosome, carries out a cascad ... | 2012 | 22902563 |
| solution structural analysis of the single-domain parvulin tbpin1. | pin1-type parvulins are phosphorylation-dependent peptidyl-prolyl cis-trans isomerases. their functions have been widely reported to be involved in a variety of cellular responses or processes, such as cell division, transcription, and apoptosis, as well as in human diseases including alzheimer's disease and cancers. tbpin1 was identified as a novel class of pin1-type parvulins from trypanosoma brucei, containing a unique ppiase domain, which can catalyze the isomerization of phosphorylated ser/ ... | 2012 | 22900083 |
| functional characterization of two paralogs that are novel rna binding proteins influencing mitochondrial transcripts of trypanosoma brucei. | a majority of trypanosoma brucei proteins have unknown functions, a consequence of its independent evolutionary history within the order kinetoplastida that allowed for the emergence of several unique biological properties. among these is rna editing, needed for expression of mitochondrial-encoded genes. the recently discovered mitochondrial rna binding complex 1 (mrb1) is composed of proteins with several functions in processing organellar rna. we characterize two mrb1 subunits, referred to her ... | 2012 | 22898985 |
| conventional therapy and promising plant-derived compounds against trypanosomatid parasites. | leishmaniasis and trypanosomiasis are two neglected and potentially lethal diseases that affect mostly the poor and marginal populations of developing countries around the world and consequently have an important impact on public health. clinical manifestations such as cutaneous, mucocutaneous, and visceral disorders are the most frequent forms of leishmaniasis, a group of diseases caused by several leishmania spp. american trypanosomiasis, or chagas disease, is caused by trypanosoma cruzi, a pa ... | 2012 | 22888328 |
| rapid calculation of protein chemical shifts using bond polarization theory and its application to protein structure refinement. | although difficult to analyze, nmr chemical shifts provide detailed information on protein structure. we have adapted the semi-empirical bond polarization theory (bpt) to protein chemical shift calculation and chemical shift driven protein structure refinement. a new parameterization for bpt amide nitrogen chemical shift calculation has been derived from mp2 ab initio calculations and successfully evaluated using crystalline tripeptides. we computed the chemical shifts of the small globular prot ... | 2012 | 22868284 |
| regulation of the cell division cycle in trypanosoma brucei. | the cell division cycle is tightly regulated by the activation and inactivation of a series of proteins that control the replication and segregation of organelles to the daughter cells. during the past decade, we have witnessed significant advances in our understanding of the cell cycle in trypanosoma brucei and how the cycle is regulated by various regulatory proteins. however, many other regulators, especially those unique to trypanosomes, remain to be identified, and we are just beginning to ... | 2012 | 22865501 |
| a novel association between two trypanosome-specific factors and the conserved l5-5s rrna complex. | p34 and p37 are two previously identified rna binding proteins in the flagellate protozoan trypanosoma brucei. rna interference studies have determined that the proteins are involved in and essential for ribosome biogenesis. the proteins interact with the 5s rrna with nearly identical binding characteristics. we have shown that this interaction is achieved mainly through the loopa region of the rna, but p34 and p37 also protect the l5 binding site located on loopc. we now provide evidence to sho ... | 2012 | 22859981 |
| comparative serum biochemical changes induced by experimental infection of t. brucei and t. congolense in pigs. | a comparative evaluation of the serum biochemical parameters was carried out in groups of young pigs aged 3-5 months experimentally infected with single infection of trypanosoma brucei, trypanosoma congolense, and a mixed infection of the two species. all the parameters studied (alanine amino transferase, aspartate amino transferase, albumin, globulin, cholesterol and creatinine) with the exception of total protein and urea varied significantly (p<0.05) between the infected groups and uninfected ... | 2012 | 22858639 |
| chemical, genetic and structural assessment of pyridoxal kinase as a drug target in the african trypanosome. | pyridoxal-5'-phosphate (vitamin b(6) ) is an essential cofactor for many important enzymatic reactions such as transamination and decarboxylation. african trypanosomes are unable to synthesise vitamin b(6) de novo and rely on uptake of b(6) vitamers such as pyridoxal and pyridoxamine from their hosts, which are subsequently phosphorylated by pyridoxal kinase (pdxk). a conditional null mutant of pdxk was generated in trypanosoma brucei bloodstream forms showing that this enzyme is essential for g ... | 2012 | 22857512 |
| human african trypanosomiasis in a traveler: diagnostic pitfalls. | abstract. an israeli traveler returning from tanzania presented with a relapsing febrile illness. a diagnosis of trypanosoma brucei rhodesiense infection was established by blood smear after nearly a month. blood polymerase chain reaction failed to provide an early diagnosis of human african trypanososmiasis. recognition of suggestive signs should prompt physicians to perform repeated tests before ruling out human african trypanososmiasis. | 2012 | 22855756 |
| identification of selective tubulin inhibitors as potential anti-trypanosomal agents. | the potency of a series of sulfonamide tubulin inhibitors against the growth of trypanosoma brucei (t. brucei), as well as human cancer and primary fibroblast cells were evaluated with the aim of determining whether compounds that selectively inhibit parasite proliferation could be identified. several compounds showed excellent selectivity against t. brucei growth, and have the potential to be used for the treatment of human african trypanosomiasis. a t. brucei tubulin protein homology model was ... | 2012 | 22850214 |
| pharmacology of db844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human african trypanosomiasis. | novel drugs to treat human african trypanosomiasis (hat) are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (nect) to who model lists of essential medicines against second stage hat, where parasites have invaded the central nervous system (cns). the pharmacology of a potential orally available lead compound, n-methoxy-6-{5-[4-(n-methoxyamidino) phenyl]-furan-2-yl}-nicotinamidine (db844), was evaluated in a vervet monkey model of second stage hat, ... | 2012 | 22848769 |
| in-silico investigation of antitrypanosomal phytochemicals from nigerian medicinal plants. | human african trypanosomiasis (hat), a parasitic protozoal disease, is caused primarily by two subspecies of trypanosoma brucei. hat is a re-emerging disease and currently threatens millions of people in sub-saharan africa. many affected people live in remote areas with limited access to health services and, therefore, rely on traditional herbal medicines for treatment. | 2012 | 22848767 |
| trypanosoma brucei has a canonical mitochondrial processing peptidase. | most mitochondrial matrix and inner membrane proteins have n-terminal presequences which serve as import signals. after import these presequences are cleaved by the heterodimeric mitochondrial processing peptidase. in the parasitic protozoa trypanosoma brucei mitochondrial protein import relies on presequences that are much shorter than in other eukaryotes. how they are processed is unknown. the trypansomal genome encodes four open reading frames that are annotated as mitochondrial processing pe ... | 2012 | 22841752 |
| genome-wide analysis reveals extensive functional interaction between dna replication initiation and transcription in the genome of trypanosoma brucei. | identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. transcription of the trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. to understand how dna replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator orc1/cdc6 and have identified replication origins, revealing tha ... | 2012 | 22840408 |
| cinnamoylphenethyl amides from polygonum hyrcanicum possess anti-trypanosomal activity. | a methanolic extract from aerial parts of polygonum hyrcanicum (polygonaceae) showed high activity against trypanosoma brucei rhodesiense (ic50 = 3.7 microg/ml). bioassay-guided fractionation of the extract resulted in isolation of cinnamoylphenethyl amides, including n-trans-caffeoyltyramine (1), n-trans-p-coumaroyltyramine (7), and n-trans-feruloyltyramine (8) as the main active constituents (ic50s ranging from 2.2 to 13.3 microm). some structurally related, but less active compounds, such as ... | 2012 | 22816300 |
| cerebrospinal fluid neopterin as marker of the meningo-encephalitic stage of trypanosoma brucei gambiense sleeping sickness. | sleeping sickness, or human african trypanosomiasis (hat), is a protozoan disease that affects rural communities in sub-saharan africa. determination of the disease stage, essential for correct treatment, represents a key issue in the management of patients. in the present study we evaluated the potential of cxcl10, cxcl13, icam-1, vcam-1, mmp-9, b2mg, neopterin and igm to complement current methods for staging trypanosoma brucei gambiense patients. | 2012 | 22815865 |
| studies on the organization of the docking complex involved in matrix protein import into glycosomes of trypanosoma brucei. | trypanosoma brucei contains peroxisome-like organelles designated glycosomes because they sequester the major part of the glycolytic pathway. import of proteins into the peroxisomal matrix involves a protein complex associated with the peroxisomal membrane of which pex13 is a component. two very different pex13 isoforms have recently been identified in t. brucei. a striking feature of one of the isoforms, tbpex13.1, is the presence of a c-terminal type 1 peroxisomal-targeting signal (pts1), the ... | 2012 | 22809509 |
| trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the hphb receptor implicated in human serum resistance. | trypanosoma brucei rhodesiense (tbr) and t. b. gambiense (tbg), causative agents of human african trypanosomiasis (sleeping sickness) in africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (tlfs), components of innate immunity in human serum that protect against infection by other african trypanosomes. in tbr, lytic activity is suppressed by the tbr-specific serum-resistance associated (sra) protein. the mechanism in tbg is less well understood but ... | 2012 | 22802982 |
| multifunctional g-rich and rrm-containing domains of tbrgg2 perform separate yet essential functions in trypanosome rna editing. | efficient editing of trypanosoma brucei mitochondrial rnas involves the actions of multiple accessory factors. t. brucei rgg2 (tbrgg2) is an essential protein crucial for initiation and 3'-to-5' progression of editing. tbrgg2 comprises an n-terminal g-rich region containing gwg and rg repeats and a c-terminal rna recognition motif (rrm)-containing domain. here, we perform in vitro and in vivo separation-of-function studies to interrogate the mechanism of tbrgg2 action in rna editing. tbrgg2 pref ... | 2012 | 22798390 |
| bacterial origin of a mitochondrial outer membrane protein translocase: new perspectives from comparative single channel electrophysiology. | mitochondria are of bacterial ancestry and have to import most of their proteins from the cytosol. this process is mediated by tom40, an essential protein that forms the protein-translocating pore in the outer mitochondrial membrane. tom40 is conserved in virtually all eukaryotes, but its evolutionary origin is unclear because bacterial orthologues have not been identified so far. recently, it was shown that the parasitic protozoon trypanosoma brucei lacks a conventional tom40 and instead employ ... | 2012 | 22778261 |
| trypanosoma brucei transferrin receptor can bind c-lobe and n-lobe fragments of transferrin. | transferrin (tf) is a dumbbell-shaped iron transport protein composed of two homologous lobes (c-lobe and n-lobe) and is an essential growth factor for the protozoan parasite trypanosoma brucei. the trypanosomal receptor for tf uptake (tbtfr) is a heterodimeric complex that bears no structural similarity with the human tf receptor. as a first step in identifying the region of tf involved in binding to the tbtfr, c-lobe and n-lobe fragments were assessed for their capability to interact with the ... | 2012 | 22776208 |
| discovery of nitroheterocycles active against african trypanosomes. in vitro screening and preliminary sar studies. | a selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite trypanosoma brucei rhodesiense, causative agent of human african trypanosomiasis (hat). the unspecific cytotoxicity of the compounds was also evaluated against rat myoblast l6-cells to measure the selectivity of the compounds towards the parasite. this screening revealed some preliminary structure-activity relationships (sar) among the series, and six hit compou ... | 2012 | 22738640 |
| structure- and ligand-based structure-activity relationships for a series of inhibitors of aldolase. | aldolase has emerged as a promising molecular target for the treatment of human african trypanosomiasis. over the last years, due to the increasing number of patients infected with trypanosoma brucei, there is an urgent need for new drugs to treat this neglected disease. in the present study, two-dimensional fragment-based quantitative-structure activity relationship (qsar) models were generated for a series of inhibitors of aldolase. through the application of leave-one-out and leave-many-out c ... | 2012 | 22734708 |
| trypanosomes lacking uracil-dna glycosylase are hypersensitive to antifolates and present a mutator phenotype. | cells contain low amounts of uracil in dna which can be the result of dutp misincorporation during replication or cytosine deamination. elimination of uracil in the base excision repair pathway yields an abasic site, which is potentially mutagenic unless repaired. the trypanosoma brucei genome presents a single uracil-dna glycosylase responsible for removal of uracil from dna. here we establish that no excision activity is detected on u:g, u:a pairs or single-strand uracil-containing dna in urac ... | 2012 | 22728162 |
| priorities for the elimination of sleeping sickness. | sleeping sickness describes two diseases, both fatal if left untreated: (i) gambian sleeping sickness caused by trypanosoma brucei gambiense, a chronic disease with average infection lasting around 3 years, and (ii) rhodesian sleeping sickness caused by t. b. rhodesiense, an acute disease with death occurring within weeks of infection. control of gambian sleeping sickness is based on case detection and treatment involving serological screening, followed by diagnostic confirmation and staging. in ... | 2012 | 22726645 |
| transcript expression analysis of putative trypanosoma brucei gpi-anchored surface proteins during development in the tsetse and mammalian hosts. | human african trypanosomiasis is a devastating disease caused by the parasite trypanosoma brucei. trypanosomes live extracellularly in both the tsetse fly and the mammal. trypanosome surface proteins can directly interact with the host environment, allowing parasites to effectively establish and maintain infections. glycosylphosphatidylinositol (gpi) anchoring is a common posttranslational modification associated with eukaryotic surface proteins. in t. brucei, three gpi-anchored major surface pr ... | 2012 | 22724039 |
| urea-based inhibitors of trypanosoma brucei methionyl-trna synthetase: selectivity and in vivo characterization. | urea-based methionyl-trna synthetase inhibitors were designed, synthesized, and evaluated for their potential toward treating human african trypanosomiasis (hat). with the aid of a homology model and a structure-activity-relationship approach, low nm inhibitors were discovered that show high selectivity toward the parasite enzyme over the closest human homologue. these compounds inhibit parasite growth with ec(50) values as low as 0.15 μm while having low toxicity to mammalian cells. two compoun ... | 2012 | 22720744 |
| untreated human infections by trypanosoma brucei gambiense are not 100% fatal. | the final outcome of infection by trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. while scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years) of a cohort of 50 human african trypanosomiasis (hat) patien ... | 2012 | 22720107 |
| identification of mimotopes with diagnostic potential for trypanosoma brucei gambiense variant surface glycoproteins using human antibody fractions. | at present, screening of the population at risk for gambiense human african trypanosomiasis (hat) is based on detection of antibodies against native variant surface glycoproteins (vsgs) of trypanosoma brucei (t.b.) gambiense. drawbacks of these native vsgs include culture of infective t.b. gambiense trypanosomes in laboratory rodents, necessary for production, and the exposure of non-specific epitopes that may cause cross-reactions. we therefore aimed at identifying peptides that mimic epitopes, ... | 2012 | 22720103 |
| an alternative form of melarsoprol in sleeping sickness. | human african trypanosomiasis (hat), or sleeping sickness, is a major threat to human health throughout sub-saharan africa. almost always fatal if untreated or inadequately treated, a commonly used drug for treating late-stage hat, and the only drug for late-stage trypanosoma brucei rhodesiense, is intravenous melarsoprol, which kills 5% of patients receiving it. melarsoprol cyclodextrin inclusion complexes have been tested in a highly reliable mouse model of hat. these complexes increase the or ... | 2012 | 22704910 |
| adenylate cyclases of trypanosoma brucei inhibit the innate immune response of the host. | the parasite trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases. activation of these enzymes requires the dimerization of the catalytic domain and typically occurs under stress. using a dominant-negative strategy, we found that reducing adenylate cyclase activity by about 50% allowed trypanosome growth but reduced the parasite's ability to control the early innate immune defense of the host. specifically, activation of trypanosome adenylate cyclase resu ... | 2012 | 22700656 |
| comparative serum biochemical changes in mongrel dogs following single and mixed infections of trypanosoma congolense and trypanosoma brucei brucei. | the serum activities of alkaline phosphatase (ap), alanine aminotransferase (alt), aspartate aminotransferase (ast) and the serum levels of conjugated bilirubin (cb), blood urea nitrogen (bun) and creatinine were studied following single and mixed infections of mongrel dogs with trypanosoma congolense and trypanosoma brucei brucei. twenty mongrel dogs of both sexes aged between 3 and 6 months, and weighing between 2.5 and 5.9 kg were used for the study. the dogs were kept in clean metal cages in ... | 2012 | 22694831 |
| apol1 expression is induced by trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness. | most african trypanosome species are sensitive to trypanolytic factors (tlfs) present in human serum. trypanosome lysis was demonstrated to be associated with apolipoprotein l-i (apol1). trypanosoma brucei (t. b.) gambiense and trypanosoma brucei rhodesiense, the two human infective trypanosome species, have both developed distinct resistance mechanisms to apol1 mediated lysis. whereas t. b. rhodesiense resistance is linked with the expression of the serum resistance associated (sra) protein tha ... | 2012 | 22691369 |
| identification of the regulatory elements controlling the transmission stage-specific gene expression of pad1 in trypanosoma brucei. | trypanosomatid parasites provide an extreme model for the posttranscriptional control of eukaryotic gene expression. however, most analysis of their differential gene regulation has focussed on comparisons between life-cycle stages that exist in the blood of mammalian hosts and tsetse flies, the parasite's vector. these environments differ acutely in their temperature, and nutritional, metabolic and molecular composition. in the bloodstream, however, a more exquisitely regulated developmental st ... | 2012 | 22684509 |
| iotrochamides a and b, antitrypanosomal compounds from the australian marine sponge iotrochota sp. | bioassay-guided isolation of the ch(2)cl(2)/meoh extract from the australian sponge iotrochota sp. resulted in the purification of two new n-cinnamoyl-amino acids, iotrochamides a (1) and b (2). the chemical structures of 1 and 2 were determined by 1d/2d nmr and ms data analyses. compounds 1 and 2 were shown to inhibit trypanosoma brucei brucei with ic(50) values of 3.4 and 4.7 μm, respectively. | 2012 | 22677313 |
| trypanosoma brucei 20 s editosomes have one rna substrate-binding site and execute rna unwinding activity. | editing of mitochondrial pre-mrnas in african trypanosomes generates full-length transcripts by the site-specific insertion and deletion of uridylate nucleotides. the reaction is catalyzed by a 0.8 mda multienzyme complex, the editosome. although the binding of substrate pre-edited mrnas and cognate guide rnas (grnas) represents the first step in the reaction cycle, the biochemical and biophysical details of the editosome/rna interaction are not understood. here we show that editosomes bind full ... | 2012 | 22661715 |
| spliced leader rna silencing (sls) - a programmed cell death pathway in trypanosoma brucei that is induced upon er stress. | trypanosoma brucei is the causative agent of african sleeping sickness. the parasite cycles between its insect (procyclic form) and mammalian hosts (bloodstream form). trypanosomes lack conventional transcription regulation, and their genes are transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. in trans-splicing, which is essential for processing of each mrna, an exon, the spliced leader (sl) is added to all mrnas from a small rna, the sl rna. trypanosom ... | 2012 | 22650251 |
| a modular and optimized single marker system for generating trypanosoma brucei cell lines expressing t7 rna polymerase and the tetracycline repressor. | here, we present a simple modular extendable vector system for introducing the t7 rna polymerase and tetracycline repressor genes into trypanosoma brucei. this novel system exploits developments in our understanding of gene expression and genome organization to produce a streamlined plasmid optimized for high levels of expression of the introduced transgenes. we demonstrate the utility of this novel system in bloodstream and procyclic forms of trypanosoma brucei, including the genome strain treu ... | 2012 | 22645659 |
| trypanosomes contain two highly different isoforms of peroxin pex13 involved in glycosome biogenesis. | we previously identified the peroxin pex13 in trypanosoma brucei. although lacking some features considered typical of pex13s, it appeared functional in the biogenesis of glycosomes, the peroxisome-like organelles of trypanosomatids. here we report the identification of a very different trypanosomatid pex13, not containing the commonly encountered pex13 sh3 domain but having other typical features. it is readily detected with the jackhmmer database search program, but not with psi-blast. this is ... | 2012 | 22641036 |
| human african trypanosomiasis. | human african trypanosomiasis (sleeping sickness) is caused by the unicellular parasite trypanosoma brucei and transmitted by tsetse flies. it occurs exclusively in sub-saharan africa, usually in rural areas affected by civil conflicts and neglected health systems. reported cases are fewer than 10,000/year, which classifies it as one of the most neglected tropical diseases. because sleeping sickness is fatal if not treated, it has to be included in the differential diagnosis of every febrile tra ... | 2012 | 22632638 |
| additive and transcript-specific effects of kpap1 and tbrnd activities on 3' non-encoded tail characteristics and mrna stability in trypanosoma brucei. | short, non-encoded oligo(a), oligo(u), or a/u tails can impact mrna stability in kinetoplastid mitochondria. however, a comprehensive picture of the relative effects of these modifications in rna stability is lacking. furthermore, while the u-preferring exoribonuclease tbrnd acts on u-tailed grnas, its role in decay of uridylated mrnas has only been cursorily investigated. here, we analyzed the roles of mrna 3' tail composition and tbrnd in rna decay using cells harbouring single or double knock ... | 2012 | 22629436 |
| a quantitative 3d motility analysis of trypanosoma brucei by use of digital in-line holographic microscopy. | we present a quantitative 3d analysis of the motility of the blood parasite trypanosoma brucei. digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. differences in the motili ... | 2012 | 22629379 |
| an orphan kinesin in trypanosomes cooperates with a kinetoplastid-specific kinesin to maintain cell morphology by regulating subpellicular microtubules. | microtubules are a vital part of the cytoskeleton of eukaryotic cells and are involved in various cellular processes. the cytoskeleton of trypanosoma brucei is characterized by an array of subpellicular microtubules and is essential for maintenance of cell shape and polarity, but little is known about the regulation of the assembly and organization of the subpellicular microtubule corset. here, we report that the orphan kinesin tbkin-d regulates the organization of subpellicular microtubules and ... | 2012 | 22623724 |
| extra-glycosomal localisation of trypanosoma brucei hexokinase 2. | the majority of the glycolytic enzymes in the african trypanosome are compartmentalised within peroxisome-like organelles, the glycosomes. polypeptides harbouring peroxisomal targeting sequences (pts type 1 or 2) are targeted to these organelles. this targeting is essential to parasite viability, as compartmentalisation of glycolytic enzymes prevents unregulated atp-dependent phosphorylation of intermediate metabolites. here, we report the surprising extra-glycosomal localisation of a pts-2 bear ... | 2012 | 22619756 |
| modeling the control of trypanosomiasis using trypanocides or insecticide-treated livestock. | in uganda, rhodesian sleeping sickness, caused by trypanosoma brucei rhodesiense, and animal trypanosomiasis caused by t. vivax and t. congolense, are being controlled by treating cattle with trypanocides and/or insecticides. we used a mathematical model to identify treatment coverages required to break transmission when host populations consisted of various proportions of wild and domestic mammals, and reptiles. | 2012 | 22616017 |
| characterization of trypanosoma brucei gambiense variant surface glycoprotein litat 1.5. | at present, all available diagnostic antibody detection tests for trypanosoma brucei gambiense human african trypanosomiasis are based on predominant variant surface glycoproteins (vsgs), such as vsg litat 1.5. during investigations aiming at replacement of the native vsgs by recombinant proteins or synthetic peptides, the sequence of vsg litat 1.5 was derived from cdna and direct n-terminal amino acid sequencing. characterization of the vsg based on cysteine distribution in the amino acid seque ... | 2012 | 22614354 |
| a role for the vesicle-associated tubulin binding protein arl6 (bbs3) in flagellum extension in trypanosoma brucei. | the small gtpase arl6 is implicated in the ciliopathic human genetic disorder bardet-biedl syndrome, acting at primary cilia in recruitment of the octomeric bbsome complex, which is required for specific trafficking events to and from the cilium in eukaryotes. here we describe functional characterisation of arl6 in the flagellated model eukaryote trypanosoma brucei, which requires motility for viability. unlike human arl6 which has a ciliary localisation, tbarl6 is associated with electron-dense ... | 2012 | 22609302 |
| new insights in staging and chemotherapy of african trypanosomiasis and possible contribution of medicinal plants. | human african trypanosomiasis (hat) is a fatal if untreated fly-borne neuroinflammatory disease caused by protozoa of the species trypanosoma brucei (t.b.). the increasing trend of hat cases has been reversed, but according to who experts, new epidemics of this disease could appear. in addition, hat is still a considerable burden for life quality and economy in 36 sub-saharan africa countries with 15-20 million persons at risk. following joined initiatives of who and private partners, the fight ... | 2012 | 22593674 |
| mechanism for activation of triosephosphate isomerase by phosphite dianion: the role of a hydrophobic clamp. | the role of the hydrophobic side chains of ile-172 and leu-232 in catalysis of the reversible isomerization of r-glyceraldehyde 3-phosphate (gap) to dihydroxyacetone phosphate (dhap) by triosephosphate isomerase (tim) from trypanosoma brucei brucei (tbb) has been investigated. the i172a and l232a mutations result in 100- and 6-fold decreases in k(cat)/k(m) for the isomerization reaction, respectively. the effect of the mutations on the product distributions for the catalyzed reactions of gap and ... | 2012 | 22583393 |
| proliferating bloodstream-form trypanosoma brucei use a negligible part of consumed glucose for anabolic processes. | our quantitative knowledge of carbon fluxes in the long slender bloodstream form (bsf) trypanosoma brucei is mainly based on non-proliferating parasites, isolated from laboratory animals and kept in buffers. in this paper we present a carbon balance for exponentially growing bloodstream form trypanosomes. the cells grew with a doubling time of 5.3h, contained 46 μ mol of carbon (10(8) cells)(-1) and had a glucose consumption flux of 160 nmol min(-1) (10(8) cells)(-1). the molar ratio of pyruvate ... | 2012 | 22580731 |
| comparative silac proteomic analysis of trypanosoma brucei bloodstream and procyclic lifecycle stages. | the protozoan parasite trypanosoma brucei has a complex digenetic lifecycle between a mammalian host and an insect vector, and adaption of its proteome between lifecycle stages is essential to its survival and virulence. we have optimized a procedure for growing trypanosoma brucei procyclic form cells in conditions suitable for stable isotope labeling by amino acids in culture (silac) and report a comparative proteomic analysis of cultured procyclic form and bloodstream form t. brucei cells. in ... | 2012 | 22574199 |
| selective blockade of trypanosomatid protein synthesis by a recombinant antibody anti-trypanosoma cruzi p2β protein. | the ribosomal p proteins are located on the stalk of the ribosomal large subunit and play a critical role during the elongation step of protein synthesis. the single chain recombinant antibody c5 (scfv c5) directed against the c-terminal region of the trypanosoma cruzi p2β protein (tcp2β) recognizes the conserved c-terminal end of all t. cruzi ribosomal p proteins. although this region is highly conserved among different species, surface plasmon resonance analysis showed that the scfv c5 possess ... | 2012 | 22570698 |
| disparate phenotypic effects from the knockdown of various trypanosoma brucei cytochrome c oxidase subunits. | the trypanosoma brucei cytochrome c oxidase (respiratory complex iv) is a very divergent complex containing a surprisingly high number of trypanosomatid-specific subunits with unknown function. to gain insight into the functional organization of this large protein complex, the expression of three novel subunits (tbcox vii, tbcox x and tbcox 6080) were down-regulated by rna interference. we demonstrate that all three subunits are important for the proper function of complex iv and the growth of t ... | 2012 | 22569586 |
| untargeted metabolomics reveals a lack of synergy between nifurtimox and eflornithine against trypanosoma brucei. | a non-targeted metabolomics-based approach is presented that enables the study of pathways in response to drug action with the aim of defining the mode of action of trypanocides. eflornithine, a polyamine pathway inhibitor, and nifurtimox, whose mode of action involves its metabolic activation, are currently used in combination as first line treatment against stage 2, cns-involved, human african trypanosomiasis (hat). drug action was assessed using an lc-ms based non-targeted metabolomics approa ... | 2012 | 22563508 |
| editosome accessory factors krepb9 and krepb10 in trypanosoma brucei. | multiprotein complexes, called editosomes, catalyze the uridine insertion and deletion rna editing that forms translatable mitochondrial mrnas in kinetoplastid parasites. we have identified here two new u1-like zinc finger proteins that associate with editosomes and have shown that they are related to krepb6, krepb7, and krepb8, and thus we have named them kinetoplastid rna editing proteins, krepb9 and krepb10. they are conserved and syntenic in trypanosomatids although krepb10 is absent in tryp ... | 2012 | 22562468 |
| the structure of the c-terminal domain of the largest editosome interaction protein and its role in promoting rna binding by rna-editing ligase l2. | trypanosomatids, such as the sleeping sickness parasite trypanosoma brucei, contain a ∼ 20s rna-editing complex, also called the editosome, which is required for u-insertion/deletion editing of mitochondrial mrnas. the editosome contains a core of 12 proteins including the large interaction protein a1, the small interaction protein a6, and the editing rna ligase l2. using biochemical and structural data, we identified distinct domains of t. brucei a1 which specifically recognize a6 and l2. we pr ... | 2012 | 22561373 |
| trypanosoma brucei: chemical evidence that cathepsin l is essential for survival and a relevant drug target. | the protozoan parasite causing human african trypanosomiasis, trypanosoma brucei, displays cysteine peptidase activity, the chemical inhibition of which is lethal to the parasite. this activity comprises a cathepsin b (tbcatb) and a cathepsin l (tbcatl). previous rna interference (rnai) data suggest that tbcatb rather than tbcatl is essential to survival even though silencing of the latter was incomplete. also, chemical evidence supporting the essentiality of either enzyme which would facilitate ... | 2012 | 22549023 |
| trypanosomal immune evasion, chronicity and transmission: an elegant balancing act. | during their life cycle, trypanosomes must overcome conflicting demands to ensure their survival and transmission. first, they must evade immunity without overwhelming the host. second, they must generate and maintain transmission stages at sufficient levels to allow passage into their tsetse vector. finally, they must rapidly commit to onward development when they enter the tsetse fly. on the basis of recent quantification and modelling of trypanosoma brucei infection dynamics, we propose that ... | 2012 | 22543519 |
| crystal structure of a trypanosoma brucei metacaspase. | metacaspases are distantly related caspase-family cysteine peptidases implicated in programmed cell death in plants and lower eukaryotes. they differ significantly from caspases because they are calcium-activated, arginine-specific peptidases that do not require processing or dimerization for activity. to elucidate the basis of these differences and to determine the impact they might have on the control of cell death pathways in lower eukaryotes, the previously undescribed crystal structure of a ... | 2012 | 22529389 |
| elements of nucleotide specificity in the trypanosoma brucei mitochondrial rna editing enzyme ret2. | the causative agent of african sleeping sickness, trypanosoma brucei , undergoes an unusual mitochondrial rna editing process that is essential for its survival. rna editing terminal uridylyl transferase 2 of t. brucei (tbret2) is an indispensable component of the editosome machinery that performs this editing. tbret2 is required to maintain the vitality of both the insect and bloodstream forms of the parasite, and with its high-resolution crystal structure, it poses as a promising pharmaceutica ... | 2012 | 22512810 |
| a new generation of t7 rna polymerase-independent inducible expression plasmids for trypanosoma brucei. | expression of transgenes is central to forward and reverse genetic analysis in trypanosoma brucei. the inducible expression of transgenes in trypanosomes is based on the tetracycline repressor binding to a tetracycline operator to prevent transcription in the absence of tetracycline. the same inducible system is used to produce double-stranded rna for rnai knockdown of target genes. this study describes a new plasmid pspr2.1 that drives consistent high-level expression of tetracycline repressor ... | 2012 | 22511983 |
| sleep and rhythm changes at the time of trypanosoma brucei invasion of the brain parenchyma in the rat. | human african trypanosomiasis (hat), or sleeping sickness, is a severe disease caused by trypanosoma brucei (t.b.). the disease hallmark is sleep alterations. brain involvement in hat is a crucial pathogenetic step for disease diagnosis and therapy. in this study, a rat model of african trypanosomiasis was used to assess changes of sleep-wake, rest-activity, and body temperature rhythms in the time window previously shown as crucial for brain parenchyma invasion by t.b. to determine potential bi ... | 2012 | 22497431 |
| modeling of the n-glycosylated transferrin receptor suggests how transferrin binding can occur within the surface coat of trypanosoma brucei. | the transferrin receptor of bloodstream form trypanosoma brucei is a heterodimer encoded by expression site associated genes 6 and 7. this low-abundance glycoprotein with a single glycosylphosphatidylinositol membrane anchor and eight potential n-glycosylation sites is located in the flagellar pocket. the receptor is essential for the parasite, providing its only source of iron by scavenging host transferrin from the bloodstream. here, we demonstrate that both receptor subunits contain endoglyco ... | 2012 | 22496646 |
| design, synthesis and biological evaluation of potent azadipeptide nitrile inhibitors and activity-based probes as promising anti-trypanosoma brucei agents. | trypanosoma cruzi and trypanosoma brucei are parasites that cause chagas disease and african sleeping sickness, respectively. there is an urgent need for the development of new drugs against both diseases due to the lack of adequate cures and emerging drug resistance. one promising strategy for the discovery of small-molecule therapeutics against parasitic diseases has been to target the major cysteine proteases such as cruzain for t. cruzi, and rhodesain/tbcatb for t. brucei. azadipeptide nitri ... | 2012 | 22488888 |
| the molecular dynamics of trypanosoma brucei udp-galactose 4'-epimerase: a drug target for african sleeping sickness. | during the past century, several epidemics of human african trypanosomiasis, a deadly disease caused by the protist trypanosoma brucei, have afflicted sub-saharan africa. over 10 000 new victims are reported each year, with hundreds of thousands more at risk. as current drug treatments are either highly toxic or ineffective, novel trypanocides are urgently needed. the t. brucei galactose synthesis pathway is one potential therapeutic target. although galactose is essential for t. brucei survival ... | 2012 | 22487100 |
| the origins of the trypanosome genome strains trypanosoma brucei brucei treu 927, t. b. gambiense dal 972, t. vivax y486 and t. congolense il3000. | the genomes of several tsetse-transmitted african trypanosomes (trypanosoma brucei brucei, t. b. gambiense, t. vivax, t. congolense) have been sequenced and are available to search online. the trypanosome strains chosen for the genome sequencing projects were selected because they had been well characterised in the laboratory, but all were isolated several decades ago. the purpose of this short review is to provide some background information on the origins and biological characterisation of the ... | 2012 | 22483376 |
| nup-1 is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. | a unifying feature of eukaryotic nuclear organization is genome segregation into transcriptionally active euchromatin and transcriptionally repressed heterochromatin. in metazoa, lamin proteins preserve nuclear integrity and higher order heterochromatin organization at the nuclear periphery, but no non-metazoan lamin orthologues have been identified, despite the likely presence of nucleoskeletal elements in many lineages. this suggests a metazoan-specific origin for lamins, and therefore that di ... | 2012 | 22479148 |
| proteomics and the trypanosoma brucei cytoskeleton: advances and opportunities. | trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan africa. the pathogenicity and growth of the parasite are intimately linked to its shape and form. this is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. the parasite undergoes extreme changes in cellular morphology during its l ... | 2012 | 22475638 |
| antitrypanosomal properties of panax ginseng c. a. meyer: new possibilities for a remarkable traditional drug. | african trypanosomiasis is still a major health problem in many sub-saharan countries in africa. we investigated the effects of three preparations of panax ginseng, panax notoginseng, isolated ginsenosides, and the polyacetylene panaxynol on trypanosoma brucei brucei and the human cancer cell line hela. hexane extracts and the pure panaxynol were toxic and at the same time highly selective against t. b. brucei, whereas methanol extracts and 12 isolated ginsenosides were significantly less toxic ... | 2013 | 22473703 |
| vsg 117 gene is conservatively present and early expressed in trypanosma evansi ynb stock. | african trypanosomes, including trypanosoma brucei and the closely related species trypanosoma evansi, are flagellated unicellular parasites that proliferate extracellularly in the mammalian bloodstream and tissue spaces. they evade host immune system by periodically switching their variant surface glycoprotein (vsg) coat. each trypanosome possesses a vast archive of vsgs with distinct sequence identity and different strains contain different archive of vsgs. vsg 117 was reported as a widespread ... | 2012 | 22465499 |
| a role of autophagy in trypanosoma brucei cell death. | the early branching eukaryote trypanosoma brucei contains functional autophagy machinery that allows regulated degradation of its own cellular components. in this study, we examined the function of two atg8 genes, tbatg8.1 and tbatg8.2, in starvation-induced autophagosome formation and cell death in procyclic t. brucei. upon starvation, both tbatg8.1 and tbatg8.2 localize to punctate structures characteristic of autophagosomes as shown by fluorescence and electron microscopy, and wortmannin and ... | 2012 | 22463696 |
| an essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote. | cardiolipin is important for bacterial and mitochondrial stability and function. the final step in cardiolipin biosynthesis is catalyzed by cardiolipin synthase and differs mechanistically between prokaryotes and eukaryotes. to study the importance of cardiolipin synthesis for mitochondrial integrity, membrane protein complex formation, and cell proliferation in the human and animal pathogenic protozoan parasite, trypanosoma brucei, we generated conditional cardiolipin synthase-knockout parasite ... | 2012 | 22451910 |
| the hemibiotrophic cacao pathogen moniliophthora perniciosa depends on a mitochondrial alternative oxidase for biotrophic development. | the tropical pathogen moniliophthora perniciosa causes witches' broom disease in cacao. as a hemibiotrophic fungus, it initially colonizes the living host tissues (biotrophic phase), and later grows over the dead plant (necrotrophic phase). little is known about the mechanisms that promote these distinct fungal phases or mediate the transition between them. an alternative oxidase gene (mp-aox) was identified in the m. perniciosa genome and its expression was analyzed througout the fungal life cy ... | 2012 | 22443281 |
| trypanosoma brucei thymidine kinase is tandem protein consisting of two homologous parts, which together enable efficient substrate binding. | trypanosoma brucei causes african sleeping sickness, a disease for which existing chemotherapies are limited by their toxicity or lack of efficacy. we have found that four parasites, including t. brucei, contain genes where two or four thymidine kinase (tk) sequences are fused into a single open reading frame. the t. brucei full-length enzyme as well as its two constituent parts, domain 1 and domain 2, were separately expressed and characterized. of potential interest for nucleoside analog devel ... | 2012 | 22442154 |
| krex2 is not essential for either procyclic or bloodstream form trypanosoma brucei. | most mitochondrial mrnas in trypanosoma brucei require rna editing for maturation and translation. the edited rnas primarily encode proteins of the oxidative phosphorylation system. these parasites undergo extensive changes in energy metabolism between the insect and bloodstream stages which are mirrored by alterations in rna editing. two u-specific exonucleases, krex1 and krex2, are both present in protein complexes (editosomes) that catalyze rna editing but the relative roles of each protein a ... | 2012 | 22438925 |
| human african trypanosomiasis in a belgian traveller returning from the masai mara area, kenya, february 2012. | a belgian traveller was diagnosed with human african trypanosomiasis (hat) due to trypanosoma brucei rhodesiense nine days after visiting the masai mara area in kenya. he presented with an inoculation chancre and was treated with suramin within four days of fever onset. two weeks earlier, hat was also reported in a german traveller who had visited the masai mara area. because no cases have occurred in the area for over 12 years, this may indicate a focal cluster of hat. | 2012 | 22433595 |
| trypanosoma brucei rhodesiense infection in a german traveller returning from the masai mara area, kenya, january 2012. | in january 2012, a case of human african trypanosomiasis (hat) has been identified in germany in a traveller returning from the masai mara area in kenya. the 62-year-old man had travelled to the masai mara game park from 18 to 19 january 2012 and developed fever on 28 january. the infection with trypanosoma brucei rhodesiense was confirmed by laboratory testing three days hereafter. | 2012 | 22433594 |