| trypanosoma musculi infection in mice critically relies on mannose receptor-mediated arginase induction by a tbkhc1 kinesin h chain homolog. | arginase activity induction in macrophages is an escape mechanism developed by parasites to cope with the host's immune defense and benefit from increased host-derived growth factor production. we report that arginase expression and activity were induced in macrophages during mouse infection by trypanosoma musculi, a natural parasite of this host. this induction was reproduced in vitro by excreted/secreted factors of the parasite. a mab directed to tbkhc1, an orphan kinesin h chain from trypanos ... | 2017 | 28739879 |
| andrographolide induces oxidative stress-dependent cell death in unicellular protozoan parasite trypanosoma brucei. | african sleeping sickness is a parasitic disease in humans and livestock caused by trypanosoma brucei throughout sub-saharan africa. absence of appropriate vaccines and prevalence of drug resistance proclaim that a new way of therapeutic interventions is essential against african trypanosomiasis. in the present study, we have looked into the effect of andrographolide (andro), a diterpenoid lactone from andrographis paiculata on trypanosoma brucei pra 380. although andro has been recognized as a ... | 2017 | 28739368 |
| trypanosoma brucei growth control by tnf in mammalian host is independent of the soluble form of the cytokine. | infection of c57bl/6 mice by pleomorphic african trypanosomes trypanosoma brucei and t. congolense is characterized by parasitemia waves coupled with the production of systemic levels of tnf. this cytokine is known to control t. brucei growth, but also to contribute to tissue damage, shortening the survival time of infected mice. using a dominant-negative version of tnf to discriminate between the effects of the membrane-form versus the soluble form of tnf, we show that the second form is involv ... | 2017 | 28733685 |
| rnai screening identifies trypanosoma brucei stress response protein kinases required for survival in the mouse. | protein kinases (pks) are a class of druggable targets in trypanosoma brucei, the causative agent of human african trypanosomiasis (sleeping sickness), yet little is known about which pks are essential for survival in mammals. a recent kinome-wide rnai screen with 176 individual bloodstream form trypanosoma brucei lines identified pks required for proliferation in culture. in order to assess which pks are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice ... | 2017 | 28733613 |
| novel 1,2-dihydroquinazolin-2-ones: design, synthesis, and biological evaluation against trypanosoma brucei. | in 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from glaxosmithkline against t. brucei identified 797 potent and selective hits. from this rich data set, we selected neu-0001101 (1) for hit-to-lead optimization. through our preliminary compound synthesis and sar studies, we have confirmed the previously reported activity of 1 in a t. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. pyrazole 24 achieves ... | 2017 | 28729055 |
| the nuclear proteome of trypanosoma brucei. | trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. the parasite has a huge impact on human health both directly by causing african sleeping sickness and indirectly, by infecting domestic cattle. the biology of trypanosomes involves some highly unusual, nuclear-localised processes. these include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts ... | 2017 | 28727848 |
| a targeted delivery strategy for the development of potent trypanocides. | a new drug delivery strategy was investigated for the development of potent anti-parasitic compounds against trypanosoma brucei, the causative agent of african sleeping sickness. thus, potent in vitro hexokinase inhibitors were rendered cytotoxic by appending a tripeptide peroxosomal targeting sequence that facilitated delivery of the molecular cargo to the appropriate organelle in the parasite. | 2017 | 28726862 |
| protozoadb 2.0: a trypanosoma brucei case study. | over the last decade new species of protozoa have been sequenced and deposited in genbank. analyzing large amounts of genomic data, especially using next generation sequencing (ngs), is not a trivial task, considering that researchers used to deal or focus their studies on few genes or gene families or even small genomes. to facilitate the information extraction process from genomic data, we developed a database system called protozoadb that included five genomes of protozoa in its first version ... | 2017 | 28726736 |
| metacyclic vsg expression site promoters are recognized by the same general transcription factor that is required for rna polymerase i transcription of bloodstream expression sites. | infectious metacyclic trypanosoma brucei cells develop in the salivary glands of tsetse flies. a critical aspect of the developmental program leading to acquisition of infectivity is the synthesis of a variant surface glycoprotein (vsg) coat. metacyclic vsg genes are transcribed from a set of specialized vsg expression sites (ess) that differ from bloodstream vsg ess by being monocistronic, being significantly shorter, lacking long stretches of 70-bp repeats, and having distinct promoter sequenc ... | 2017 | 28716719 |
| the trypanosoma brucei dihydroxyacetonephosphate acyltransferase tbdat is dispensable for normal growth but important for synthesis of ether glycerophospholipids. | glycerophospholipids are the most abundant constituents of biological membranes in trypanosoma brucei, which causes sleeping sickness in humans and nagana in cattle. they are essential cellular components that fulfill various important functions beyond their structural role in biological membranes such as in signal transduction, regulation of membrane trafficking or control of cell cycle progression. our previous studies have established that the glycerol-3-phosphate acyltransferase tbgat is dis ... | 2017 | 28715456 |
| life stage-specific cargo receptors facilitate glycosylphosphatidylinositol-anchored surface coat protein transport in trypanosoma brucei. | the critical virulence factor of bloodstream-form trypanosoma brucei is the glycosylphosphatidylinositol (gpi)-anchored variant surface glycoprotein (vsg). endoplasmic reticulum (er) exit of vsg is gpi dependent and relies on a discrete subset of copii machinery (tbsec23.2/tbsec24.1). in other systems, p24 transmembrane adaptor proteins selectively recruit gpi-anchored cargo into nascent copii vesicles. trypanosomes have eight putative p24s (tberp1 to tberp8) that are constitutively expressed at ... | 2017 | 28713858 |
| inhibitors of glycosomal protein import provide new leads against trypanosomiasis. | vector-borne trypanosomatid parasite infections in tropical and sub-tropical countries constitute a major threat to humans and livestock. trypanosoma brucei parasites are transmitted by tsetse fly and lead to african sleeping sickness in humans and nagana in cattle. in latin american countries, trypanosoma cruzi infections spread by triatomine kissing bugs lead to chagas disease. various species of leishmania transmitted to humans by phlebotomine sandflies manifest in a spectrum of diseases term ... | 2017 | 28706938 |
| gt-rich promoters can drive rna pol ii transcription and deposition of h2a.z in african trypanosomes. | genome-wide transcription studies are revealing an increasing number of "dispersed promoters" that, unlike "focused promoters", lack well-conserved sequence motifs and tight regulation. dispersed promoters are nevertheless marked by well-defined chromatin structures, suggesting that specific sequence elements must exist in these unregulated promoters. here, we have analyzed regions of transcription initiation in the eukaryotic parasite trypanosoma brucei, in which rna polymerase ii transcription ... | 2017 | 28701485 |
| bistacrines as potential antitrypanosomal agents. | human african trypanosomiasis (hat) is caused by two subspecies of the genus trypanosoma, namely trypanosoma brucei rhodesiense and trypanosoma brucei gambiense. the disease is fatal if left untreated and therapy is limited due to only five non-adequate drugs currently available. in preliminary studies, dimeric tacrine derivatives were found to inhibit parasite growth with ic50-values in the nanomolar concentration range. this prompted the synthesis of a small, but smart library of monomeric and ... | 2017 | 28698054 |
| differential virulence and tsetse fly transmissibility of <i>trypanosoma congolense</i> and <i>trypanosoma brucei</i> strains. | african animal trypanosomiasis causes significant economic losses in sub-saharan african countries because of livestock mortalities and reduced productivity. trypanosomes, the causative agents, are transmitted by tsetse flies (glossina spp.). in the current study, we compared and contrasted the virulence characteristics of five trypanosoma congolense and trypanosoma brucei isolates using groups of swiss white mice (n = 6). we further determined the vectorial capacity of glossina pallidipes, for ... | 2017 | 28697609 |
| application of a simple quantum chemical approach to ligand fragment scoring for trypanosoma brucei pteridine reductase 1 inhibition. | there is a need for improved and generally applicable scoring functions for fragment-based approaches to ligand design. here, we evaluate the performance of a computationally efficient model for inhibitory activity estimation, which is composed only of multipole electrostatic energy and dispersion energy terms that approximate long-range ab initio quantum mechanical interaction energies. we find that computed energies correlate well with inhibitory activity for a compound series with varying sub ... | 2017 | 28688090 |
| steroid alkaloids from holarrhena africana with strong activity against trypanosoma brucei rhodesiense. | in our continued search for natural compounds with activity against trypanosoma brucei, causative agent of human african trypanosomiasis (hat, "sleeping sickness"), we have investigated extracts from the leaves and bark of the west african holarrhenaafricana (syn. holarrhena floribunda; apocynaceae). the extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of t. brucei rhodesiense (tbr; east african hat). bioactivity-guided chromatographi ... | 2017 | 28684718 |
| trypanosoma brucei inhibition by essential oils from medicinal and aromatic plants traditionally used in cameroon (azadirachta indica, aframomum melegueta, aframomum daniellii, clausena anisata, dichrostachys cinerea and echinops giganteus). | essential oils are complex mixtures of volatile components produced by the plant secondary metabolism and consist mainly of monoterpenes and sesquiterpenes and, to a minor extent, of aromatic and aliphatic compounds. they are exploited in several fields such as perfumery, food, pharmaceutics, and cosmetics. essential oils have long-standing uses in the treatment of infectious diseases and parasitosis in humans and animals. in this regard, their therapeutic potential against human african trypano ... | 2017 | 28684709 |
| ppr polyadenylation factor defines mitochondrial mrna identity and stability in trypanosomes. | in trypanosoma brucei, most mitochondrial mrnas undergo internal changes by rna editing and 3' end modifications. the temporally separated and functionally distinct modifications are manifested by adenylation prior to editing, and by post-editing extension of a short a-tail into a long a/u-heteropolymer. the a-tail stabilizes partially and fully edited mrnas, while the a/u-tail enables mrna binding to the ribosome. here, we identify an essential pentatricopeptide repeat-containing rna binding pr ... | 2017 | 28684539 |
| ornithine uptake and the modulation of drug sensitivity in trypanosoma brucei. | trypanosoma brucei, protozoan parasites that cause human african trypanosomiasis (hat), depend on ornithine uptake and metabolism by ornithine decarboxylase (odc) for survival. indeed, odc is the target of the who "essential medicine" eflornithine, which is antagonistic to another anti-hat drug, suramin. thus, ornithine uptake has important consequences in t. brucei, but the transporters have not been identified. we describe these amino acid transporters (aats). in a heterologous expression syst ... | 2017 | 28679527 |
| host-seeking efficiency can explain population dynamics of the tsetse fly glossina morsitans morsitans in response to host density decline. | females of all blood-feeding arthropod vectors must find and feed on a host in order to produce offspring. for tsetse-vectors of the trypanosomes that cause human and animal african trypanosomiasis-the problem is more extreme, since both sexes feed solely on blood. host location is thus essential both for survival and reproduction. host population density should therefore be an important driver of population dynamics for haematophagous insects, and particularly for tsetse, but the role of host d ... | 2017 | 28672001 |
| the double-edged sword of evolution. | two gene variants provide different levels of protection against sleeping sickness, but this comes with an increased risk of developing chronic kidney disease. | 2017 | 28671870 |
| the cytological events and molecular control of life cycle development of trypanosoma brucei in the mammalian bloodstream. | african trypanosomes cause devastating disease in sub-saharan africa in humans and livestock. the parasite lives extracellularly within the bloodstream of mammalian hosts and is transmitted by blood-feeding tsetse flies. in the blood, trypanosomes exhibit two developmental forms: the slender form and the stumpy form. the slender form proliferates in the bloodstream, establishes the parasite numbers and avoids host immunity through antigenic variation. the stumpy form, in contrast, is non-prolife ... | 2017 | 28657594 |
| conversion of procyclic-form trypanosoma brucei to the bloodstream form by transient expression of rbp10. | bloodstream-form trypanosoma brucei can lose the ability to differentiate to the procyclic form during prolonged in vitro culture. this can pose a problem during complicated genetic manipulation experiments, especially when the differentiation phenotype is under investigation. ideally, to preserve differentiation competence, parasites should be cycled after every genetic manipulation step. conversion of bloodstream-form trypanosoma brucei to the procyclic form in vitro is routine, but conversion ... | 2017 | 28651963 |
| subcellular localization of glycolytic enzymes and characterization of intermediary metabolism of trypanosoma rangeli. | trypanosoma rangeli is a hemoflagellate protist that infects wild and domestic mammals as well as humans in central and south america. although this parasite is not pathogenic for human, it is being studied because it shares with trypanosoma cruzi, the etiological agent of chagas' disease, biological characteristics, geographic distribution, vectors and vertebrate hosts. several metabolic studies have been performed with t. cruzi epimastigotes, however little is known about the metabolism of t. ... | 2017 | 28645481 |
| functional and structural analysis of at-specific minor groove binders that disrupt dna-protein interactions and cause disintegration of the trypanosoma brucei kinetoplast. | trypanosoma brucei, the causative agent of sleeping sickness (human african trypanosomiasis, hat), contains a kinetoplast with the mitochondrial dna (kdna), comprising of >70% at base pairs. this has prompted studies of drugs interacting with at-rich dna, such as the n-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1h-imidazol-2-yl)amino)-n-(4-((4,5-dihydro-1h-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [n-(3-chloro-4-((4,5-dihydro-1h-imidazol-2-yl)amino)p ... | 2017 | 28637278 |
| delineating neuroinflammation, parasite cns invasion, and blood-brain barrier dysfunction in an experimental murine model of human african trypanosomiasis. | although trypanosoma brucei spp. was first detected by aldo castellani in csf samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the cns. in this investigation, we have applied contrast-enhance magnetic resonance imaging (mri) to study the effects of trypanosome infection on the blood-brain barrier (bbb) in the well-established gvr35 mouse model of sle ... | 2017 | 28636879 |
| a comparative study of the structural dynamics of four terminal uridylyl transferases. | african trypanosomiasis occurs in 36 countries in sub-saharan africa with 10,000 reported cases annually. no definitive remedy is currently available and if left untreated, the disease becomes fatal. structural and biochemical studies of trypanosomal terminal uridylyl transferases (tutases) demonstrated their functional role in extensive uridylate insertion/deletion of rna. trypanosoma brucei rna editing tutase 1 (tbret1) is involved in guide rna 3' end uridylation and maturation, while tbret2 i ... | 2017 | 28632168 |
| case of nigeria-acquired human african trypanosomiasis in united kingdom, 2016. | human african trypanosomiasis has not been reported in nigeria since 2012. nevertheless, limitations of current surveillance programs mean that undetected infections may persist. we report a recent case of stage 2 trypanosomiasis caused by trypanosoma brucei gambiense acquired in nigeria and imported into the united kingdom. | 2017 | 28628444 |
| metabolic reprogramming during the trypanosoma brucei life cycle. | cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. the causative agent of sleeping sickness, trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. in ord ... | 2017 | 28620452 |
| structural and biochemical characterization of poly-adp-ribose polymerase from trypanosoma brucei. | trypanosoma brucei is a unicellular parasite responsible for african trypanosomiasis or sleeping sickness. it contains a single parp enzyme opposed to many higher eukaryotes, which have numerous parps. parps are responsible for a post-translational modification, adp-ribosylation, regulating a multitude of cellular events. t. brucei parp, like human parps-1-3, is activated by dna binding and it potentially functions in dna repair processes. here we characterized activation requirements, structure ... | 2017 | 28623292 |
| structural insights into the alternative oxidases: are all oxidases made equal? | the alternative oxidases (aoxs) are ubiquinol-oxidoreductases that are members of the diiron carboxylate superfamily. they are not only ubiquitously distributed within the plant kingdom but also found in increasing numbers within the fungal, protist, animal and prokaryotic kingdoms. although functions of aoxs are highly diverse in general, they tend to play key roles in thermogenesis, stress tolerance (through the management of radical oxygen species) and the maintenance of mitochondrial and cel ... | 2017 | 28620034 |
| the ubiquitin-conjugating enzyme cdc34 is essential for cytokinesis in contrast to putative subunits of a scf complex in trypanosoma brucei. | the ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of e1 ubiquitin activating enzymes, e2 ubiquitin conjugating enzymes, and e3 ubiquitin ligases. one of the e3 ligases known to be responsible for the ubiquitination of cell cycle regulator ... | 2017 | 28609481 |
| use of zymography in trypanosomiasis studies. | zymography assay is a semiquantitative technique, very sensitive, and commonly used to determine metalloproteinase levels in different types of biological samples, including tissues, cells, and extracts of protein. samples containing metalloproteinases are loaded onto a polyacrylamide gel containing sodium dodecyl sulphate (sds) and a specific substrate (gelatin, casein, collagen, etc.). then proteins are allowed to migrate under an electric current and the distance of migration is inversely cor ... | 2017 | 28608214 |
| characterization of recombinant trypanosoma brucei gambiense translationally controlled tumor protein (rtbgtctp) and its interaction with glossina midgut bacteria. | in humans, sleeping sickness (i.e. human african trypanosomiasis) is caused by the protozoan parasites trypanosoma brucei gambiense (tbg) in west and central africa, and t. b. rhodesiense in east africa. we previously showed in vitro that tbg is able to excrete/secrete a large number of proteins, including translationally controlled tumor protein (tctp). moreover, the tctp gene was described previously to be expressed in tbg-infected flies. aside from its involvement in diverse cellular processe ... | 2017 | 28586253 |
| targeting cysteine proteases in trypanosomatid disease drug discovery. | chagas disease and human african trypanosomiasis are endemic conditions in latin america and africa, respectively, for which no effective and safe therapy is available. efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. these enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including i ... | 2017 | 28579388 |
| applicability of plant-based products in the treatment of trypanosoma cruzi and trypanosoma brucei infections: a systematic review of preclinical in vivo evidence. | chagas disease and sleeping sickness are neglected tropical diseases closely related to poverty, for which the development of plant-derived treatments has not been a promising prospect. thus, we systematicaly review the preclinical in vivo evidence on the applicability of plant-based products in the treatment of trypanosoma cruzi and trypanosoma brucei infections. characteristics such as disease models, treatments, toxicological safety and methodological bias were analysed. we recovered 66 full ... | 2017 | 28578742 |
| chemo-enzymatic synthesis of lipid-linked glcnac2man5 oligosaccharides using recombinant alg1, alg2 and alg11 proteins. | the biosynthesis of eukaryotic lipid-linked oligosaccharides (llos) that act as donor substrates in eukaryotic protein n-glycosylation starts on the cytoplasmic side of the endoplasmic reticulum and includes the sequential addition of five mannose units to dolichol-pyrophosphate-glcnac2. these reactions are catalyzed by the alg1, alg2 and alg11 gene products and yield dol-pp-glcnac2man5, an llo intermediate that is subsequently flipped to the lumen of the endoplasmic reticulum. while the purific ... | 2017 | 28575298 |
| an essential domain of an early-diverged rna polymerase ii functions to accurately decode a primitive chromatin landscape. | a unique feature of rna polymerase ii (rna pol ii) is its long c-terminal extension, called the carboxy-terminal domain (ctd). the well-studied eukaryotes possess a tandemly repeated 7-amino-acid sequence, called the canonical ctd, which orchestrates various steps in mrna synthesis. many eukaryotes possess a ctd devoid of repeats, appropriately called a non-canonical ctd, which performs completely unknown functions. trypanosoma brucei, the etiologic agent of african sleeping sickness, deploys an ... | 2017 | 28575287 |
| backbone nmr assignments of tryparedoxin, the central protein in the hydroperoxide detoxification cascade of african trypanosomes, in the oxidized and reduced form. | tryparedoxin (tpx) is a pivotal protein in the redox-metabolism of trypanosomatid parasites. tpx has previously been identified as a potential target for drug development in the fight against human african sleeping sickness caused by trypanosoma brucei. tpx belongs to the thioredoxin superfamily and acts as an oxidoreductase in the parasite's cytoplasm. it contains a wcppc active site motif, which enables the protein to undergo thiol-disulfide exchange. to promote future protein-drug interaction ... | 2017 | 28573456 |
| parasite polyamines as pharmaceutical targets. | there is an urgent need for the identification and validation of new therapeutic targets in protozoan parasites because currently available drugs are limited in number and usefulness, and no vaccines are available. the discovery that alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, is an efficacious treatment for african sleeping sickness caused by the protozoan parasite trypanosoma brucei, has validated the polyamine pathway as a target in protozoan parasites. polyamines a ... | 2017 | 28571553 |
| polymerase chain reaction identification of trypanosoma brucei rhodesiense in wild tsetse flies from nkhotakota wildlife reserve, malawi. | trypanosoma brucei rhodesiense is the causative agent of acute human african trypanosomiasis. identification of t. b. rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessng human disease risk, and monitoring spatiotemporal trends and impact of control interventions. accurate detection and characterisation of trypanosomes in vectors relies on molecular techniques. for the first time in malawi, a molecular technique has been used to detect trypanosomes in ... | 2017 | 28567189 |
| correction for kirkham et al., "dynein light chain lc8 is required for rna polymerase i-mediated transcription in trypanosoma brucei, facilitating assembly and promoter binding of class i transcription factor a". | | 2017 | 28566454 |
| front-line glioblastoma chemotherapeutic temozolomide is toxic to trypanosoma brucei and potently enhances melarsoprol and eflornithine. | sleeping sickness is an infectious disease that is caused by the protozoan parasite trypanosoma brucei. the second stage of the disease is characterised by the parasites entering the brain. it is therefore important that sleeping sickness therapies are able to cross the blood-brain barrier. at present, only three medications for chemotherapy of the second stage of the disease are available. as these trypanocides have serious side effects and are difficult to administer, new and safe anti-trypano ... | 2017 | 28552794 |
| dose-dependent effect and pharmacokinetics of fexinidazole and its metabolites in a mouse model of human african trypanosomiasis. | human african trypanosomiasis (hat) is a neglected tropical disease, with a population of 70 million at risk. current treatment options are limited. in the search for new therapeutics, the repurposing of the broad-spectrum antiprotozoal drug fexinidazole has completed phase iii trials with the anticipation that it will be the first oral treatment for hat. this study used the recently validated bioluminescence imaging model to assess the dose and rate of kill effect of fexinidazole in infected mi ... | 2017 | 28552771 |
| the role of the zinc finger protein zc3h32 in bloodstream-form trypanosoma brucei. | kinetoplastids rely heavily on post-transcriptional mechanisms for control of gene expression, with regulation of mrna processing, translation and degradation by rna-binding proteins. zc3h32 is a cytosolic mrna-binding protein with three non-canonical ccch zinc finger domains. it is much more abundant in bloodstream-form trypanosoma brucei than in procyclic forms. tethering of zc3h32 to a reporter mrna suppressed translation and resulted in mrna degradation, and deletion analysis suggested that ... | 2017 | 28545140 |
| non-canonical binding interactions of the rna recognition motif (rrm) domains of p34 protein modulate binding within the 5s ribonucleoprotein particle (5s rnp). | rna binding proteins are involved in many aspects of rna metabolism. in trypanosoma brucei, our laboratory has identified two trypanosome-specific rna binding proteins p34 and p37 that are involved in the maturation of the 60s subunit during ribosome biogenesis. these proteins are part of the t. brucei 5s ribonucleoprotein particle (5s rnp) and p34 binds to 5s ribosomal rna (rrna) and ribosomal protein l5 through its n-terminus and its rna recognition motif (rrm) domains. we generated truncated ... | 2017 | 28542332 |
| apol1 renal risk variants have contrasting resistance and susceptibility associations with african trypanosomiasis. | reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. in populations of african ancestry, two apolipoprotein-l1 (apol1) variants with a recessive kidney disease risk, named g1 and g2, occur at high frequency. apol1 is a trypanolytic protein that confers innate resistance to most african trypanosomes, but not trypanosoma brucei rhodesiense or t.b. gambiense, which cause human african trypanosomiasis. in this case-control study, we test the preva ... | 2017 | 28537557 |
| 3d subcellular localization with superresolution array tomography on ultrathin sections of various species. | array tomography (at) is a relatively easy-to-use and yet powerful method to put molecular identity in its full ultrastructural context. ultrathin sections are stained with fluorophores and then imaged by light and afterward by electron microscopy to obtain a correlated view of a region of interest: its ultrastructure and specific staining. by combining at with high-pressure freezing for superior structural preservation and superresolution light microscopy, even small subcellular structures can ... | 2017 | 28528634 |
| anti-trypanosomal activity of cationic n-heterocyclic carbene gold(i) complexes. | two gold(i) n-heterocyclic carbene complexes 1a and 1b were tested for their anti-trypanosomal activity against trypanosoma brucei parasites. both gold compounds exhibited excellent anti-trypanosomal activity (ic50=0.9-3.0nm). the effects of the gold complexes 1a and 1b on the t. b. brucei cytoskeleton were evaluated. rapid detachment of the flagellum from the cell body occurred after treatment with the gold complexes. in addition, a quick and complete degeneration of the parasitic cytoskeleton ... | 2017 | 28522152 |
| a role for sar1 and arf1 gtpases during golgi biogenesis in the protozoan parasite trypanosoma brucei. | a single golgi stack is duplicated and partitioned into two daughter cells during the cell cycle of the protozoan parasite trypanosoma brucei the source of components required to generate the new golgi and the mechanism by which it forms are poorly understood. using photoactivatable gfp, we show that the existing golgi supplies components directly to the newly forming golgi in both intact and semipermeabilized cells. the movement of a putative glycosyltransferase, gntb, requires the sar1 and arf ... | 2017 | 28495798 |
| charting organellar importomes by quantitative mass spectrometry. | protein import into organelles is essential for all eukaryotes and facilitated by multi-protein translocation machineries. analysing whether a protein is transported into an organelle is largely restricted to single constituents. this renders knowledge about imported proteins incomplete, limiting our understanding of organellar biogenesis and function. here we introduce a method that enables charting an organelle's importome. the approach relies on inducible rnai-mediated knockdown of an essenti ... | 2017 | 28485388 |
| dynamin-like proteins in trypanosoma brucei: a division of labour between two paralogs? | dynamins and dynamin-like proteins (dlps) belong to a family of large gtpases involved in membrane remodelling events. these include both fusion and fission processes with different dynamin proteins often having a specialised function within the same organism. trypanosoma brucei is thought to have only one multifunctional dlp (tbdlp). while this was initially reported to function in mitochondrial division only, an additional role in endocytosis and cytokinesis was later also proposed. since ther ... | 2017 | 28481934 |
| optimization of a binding fragment targeting the "enlarged methionine pocket" leads to potent trypanosoma brucei methionyl-trna synthetase inhibitors. | potent inhibitors of trypanosoma brucei methionyl-trna synthetase were previously designed using a structure-guided approach. compounds 1 and 2 were the most active compounds in the cyclic and linear linker series, respectively. to further improve cellular potency, sar investigation of a binding fragment targeting the "enlarged methionine pocket" (emp) was performed. the optimization led to the identification of a 6,8-dichloro-tetrahydroquinoline ring as a favorable fragment to bind the emp. rep ... | 2017 | 28465105 |
| the canonical poly (a) polymerase pap1 polyadenylates non-coding rnas and is essential for snorna biogenesis in trypanosoma brucei. | the parasite trypanosoma brucei is the causative agent of african sleeping sickness and is known for its unique rna processing mechanisms that are common to all the kinetoplastidea including leishmania and trypanosoma cruzi. trypanosomes possess two canonical rna poly (a) polymerases (paps) termed pap1 and pap2. pap1 is encoded by one of the only two genes harboring cis-spliced introns in this organism, and its function is currently unknown. in trypanosomes, all mrnas, and non-coding rnas such a ... | 2017 | 28456523 |
| an efficient cumate-inducible system for procyclic and bloodstream form trypanosoma brucei. | in trypanosoma brucei, the tetracycline-inducible system enables tightly-regulated, highly-efficient expression of recombinant proteins or double-stranded rna in both procyclic and bloodstream form cells, providing useful molecular genetic tools to study gene functions. an alternative, vanillic acid-inducible system is recently described for procyclic t. brucei, providing ∼18-fold increase in gfp reporter expression upon induction (sunter jd. mol. biochem. parasitol. 2016, 207:45-48). here we de ... | 2017 | 28438458 |
| synthesis and biological evaluation of selective tubulin inhibitors as anti-trypanosomal agents. | african trypanosomiasis is still a threat to human health due to the severe side-effects of current drugs. we identified selective tubulin inhibitors that showed the promise to the treatment of this disease, which was based on the tubulin protein structural difference between mammalian and trypanosome cells. further lead optimization was performed in the current study to improve the efficiency of the drug candidates. we used trypanosoma brucei brucei cells as the parasite model, and human normal ... | 2017 | 28428042 |
| the chemical characterization of nigerian propolis samples and their activity against trypanosoma brucei. | profiling of extracts from twelve propolis samples collected from eight regions in nigeria was carried out using high performance liquid chromatography (lc) coupled with evaporative light scattering (elsd), ultraviolet detection (uv) and mass spectrometry (ms), gas chromatography mass spectrometry (gc-ms) and nuclear magnetic resonance spectroscopy (nmr). principal component analysis (pca) of the processed lc-ms data demonstrated the varying chemical composition of the samples. most of the sampl ... | 2017 | 28424496 |
| comparative genomics of glossina palpalis gambiensis and g. morsitans morsitans to reveal gene orthologs involved in infection by trypanosoma brucei gambiense. | blood-feeding glossina palpalis gambiense (gpg) fly transmits the single-celled eukaryotic parasite trypanosoma brucei gambiense (tbg), the second glossina fly african trypanosome pair being glossina morsitans/t.brucei rhodesiense. whatever the t. brucei subspecies, whereas the onset of their developmental program in the zoo-anthropophilic blood feeding flies does unfold in the fly midgut, its completion is taking place in the fly salivary gland where does emerge a low size metacyclic trypomasti ... | 2017 | 28421044 |
| trypanosoma brucei tbif1 inhibits the essential f1-atpase in the infectious form of the parasite. | the mitochondrial (mt) fof1-atp synthase of the digenetic parasite, trypanosoma brucei, generates atp during the insect procyclic form (pf), but becomes a perpetual consumer of atp in the mammalian bloodstream form (bf), which lacks a canonical respiratory chain. this unconventional dependence on fof1-atpase is required to maintain the essential mt membrane potential (δψm). normally, atp hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic ... | 2017 | 28414727 |
| lineage-specific proteins essential for endocytosis in trypanosomes. | clathrin-mediated endocytosis (cme) is the most evolutionarily ancient endocytic mechanism known, and in many lineages the sole mechanism for internalisation. significantly, in mammalian cells cme is responsible for the vast bulk of endocytic flux and has likely undergone multiple adaptations to accommodate specific requirements by individual species. in african trypanosomes, we previously demonstrated that cme is independent of the ap-2 adaptor protein complex, that orthologues to many of the a ... | 2017 | 28232524 |